09:00 09:15 Welcome from PHSS Chairman and UCL Q3P Course Director James Drinkwater and Professor Duncan Craig, Director UCL School of Pharmacy 09:15 10:00 Revision of Annex 1 Manufacture of sterile medicinal products – a GMP inspector’s point of view. Andrew Hopkins MHRA Senior Inspector 10:00 11:00 Panel Discussion – Annex 1 revision. Discussion panel: MHRA, PHSS, A3P, PDA, ISPE, R3 Nordic and ECA. 11:00 11:45 Coffee and Viewing Exhibitions Blue Badge - Square Lounge Green Badge - MLT Exhibition Area 11:45 12:30 Data Integrity: Considering non-conformances, challenges, requirements and impact on product/ batch release. Di Morris: GSK Global auditor, Ex-MHRA senior inspector. 12:30 13:30 Lunch and Networking 13:30 14:15 Stream 1: Main Lecture Theatre Changes and their impact in revisions of EU GMP Regulations: Orange Guide; chapters 3, 5, 8 and annex 15: Qualification and validation. Malcolm Holmes: Consultant/ Freelance GMP/ PHSS regulatory update author. 13:30 14:15 Stream 2: Workshop Room Annex 16: Certification of a Qualified person and batch release. The impact of the revision and new requirements. Richard Funnell – Funnell Pharma Consultants Ltd 14:15 14:45 Coffee and Viewing Exhibitions Blue Badge - MLT Exhibition Area Green Badge - Square Lounge 14:45 15:30 Stream 3: Main Lecture Theatre ISO 14644 (part 1 & 2) revision update. Key points about the revisions and potential impact on GMP qualification and operations. Gordon Farquharson: GMP Consultant; Critical systems 14:45 15:30 Stream 4: Workshop Room Impact of regulations in filling multiple products in the same facility, considering aseptic processing of non-hazardous product, cytotoxic products and biologically hazardous products, including live virus. James Drinkwater: F Ziel Head of Aseptic processing technologies and GMP compliance. Please hand in your feedback forms. Course notes will be sent electronically. We would be delighted to welcome your colleagues as members. Thank you for coming. PHSS Annual Conference in association with UCL Q3P UCL School of Pharmacy, London Friday 11 th September 2015 Impact of changes in GMP regulations including Annex 1 & ISO standard revisions. over 25 years of advancing pharmaceutical and healthcare sciences Distribution rights are property of the PHSS, permission must be obtained for use.
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09:00 09:15Welcome from PHSS Chairman and UCL Q3P Course Director
James Drinkwater and Professor Duncan Craig, Director UCL School of Pharmacy
09:15 10:00Revision of Annex 1 Manufacture of sterile medicinal products – a GMP inspector’s point of view.
11:00 11:45 Coffee and Viewing ExhibitionsBlue Badge - Square LoungeGreen Badge - MLT Exhibition Area
11:45 12:30
Data Integrity: Considering non-conformances, challenges, requirements and impact on product/ batch release.
Di Morris: GSK Global auditor,Ex-MHRA senior inspector.
12:30 13:30 Lunch and Networking
13:30 14:15
Stream 1: Main Lecture TheatreChanges and their impact in revisions of EU GMP Regulations: Orange Guide; chapters 3, 5, 8 and annex 15: Qualification and validation.
Stream 3: Main Lecture TheatreISO 14644 (part 1 & 2) revision update.Key points about the revisions and potential impact on GMP qualification and operations.
Gordon Farquharson: GMP Consultant; Critical systems
14:45 15:30
Stream 4: Workshop RoomImpact of regulations in filling multiple products in the same facility, considering aseptic processing of non-hazardous product, cytotoxic products and biologically hazardous products, including live virus.
James Drinkwater: F Ziel Head of Aseptic processing technologies and GMP compliance.
Please hand in your feedback forms.Course notes will be sent electronically.We would be delighted to welcome your colleagues as members.Thank you for coming.
PHSS Annual Conferencein association with UCL Q3PUCL School of Pharmacy, LondonFriday 11th September 2015
Impact of changes in GMP regulations including Annex 1 & ISO standard revisions.
over 25 years of advancing pharmaceutical and healthcare sciences
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James Drinkwater
Chairman of PHSS –
Pharmaceutical &
Healthcare Sciences Society
1
Introduction and Welcome
PHSS & UCL QP Annual Conference 2015
UCLQP3
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UCL School of Pharmacy Welcome
2
General guidance for conference:
Fire exits…. No planned fire alarm tests.
Toilets/ Rest rooms; off stair wells… directions from PHSS/ UCL staff
Blue badge and Green badge coffee break and lunch rota; Exhibitors split between break rooms. Directions from PHSS/ UCL staff.
Presentations downloaded via link provided after the conference.
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Conference Welcome
3
The PHSS wish to thank Dr. Khalid Sheikh,Director, UCL QP Course, Department of Pharmaceutics and his UCL School of Pharmacy colleagues for the collaboration with the PHSS.
Announcement: Kay O’Hagan is to take over as Editor in Chief of the EJPPS: European Journal of Parenteral & Pharmaceutical Sciences from Gordon Farquharson – Our sincere thanks to Gordon for his professionalism and dedication to the role over many years. We also take the opportunity to welcome Professor Bengt Ljungqvist from R3 Nordic to the conference. Bengt is also on the main editorial board of the EJPPS.
Announcement: Jenni Tranter is take over from Kay O’Hagan as the Vice Chairperson of the PHSS. Our good wishes to Jenni in this new role and sincere thanks to Kay who will continue on the PHSS Management team.
A special thank you to Andrew Hopkins, Senior MHRA GMP Inspector, and his colleagues at the MHRA for the continued support of the PHSS.
Thank you to our partners in collaboration, PDA, R3 Nordic, A3P, ISPE and ECA for your contribution to the Annex 1 revision discussion panel.
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Annex 1 revision Discussion panel
4
PHSS Moderator: Kay O’Hagan: Senior Qualified person, Hospira UK.
MHRA, EMA: Andrew Hopkins: Senior GMP MHRA Inspector, Head of EMA Annex 1 revision working group.
PDA Worldwide: Richard M. Johnson, President & CEO, microbiologist.PDA UK Chapter President: Dr Siegfried Schmitt Principal Consultant PAREXEL international
PHSS: Di Morris: GSK Compliance Audit Manager, Compliance Audit Group (CAG), Quality Systems and Compliance. PHSS Management team member.PHSS: James Drinkwater: F Ziel GmbH, Head of Aseptic processing Technologies & GMP compliance. Chairman of PHSS.
ISPE/ ISO: Gordon Farquharson: Chair BSI LBI030, Chair CEN TC243, Convenor ISO TC209 wg1, and member ISPE Sterile and HVAC CoP. Consultant Critical systems.
A3P France: Dr Roland Guinet, Ex AFFSAPS GMP Inspector, WHO GMP auditor, GMP Consultant, University Professor of Microbiology, Head of A3P Annex 1 Interest group.
R3 Nordic: Berit Reinmüller, PhD, Associate Professor in Safety Ventilation, Chalmers University of Technology, Gothenburg, Sweden, R3 Nordic journal editor.
ECA (European Compliance Academy): Dr Jean-Denis Mallet, NNE Pharmaplan, Senior Technology Partner, GMP Expertise, QP, Pharmacist. Head of ECA annex 1 comment working group.
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GMP Change and impact
5
GMP Annex’s
have changed
or are
changing;
Annex 1
Product
profiles are
changing: more
biologicals
ISO 14644‐1&2ISO 14698Revisions
GMP Chapters have
changed
The challenge
of change
through
advancement
Targeted delivery systems &
improved efficacy
Improved efficiencies, cost
reductions and competitiveness
New
Technologies
and practice
IMPACT
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6
Risk based initiatives –
science based processes
Impact of GMP regulation + ISO Standard revisions
EU GMP
ANNEX 1,
15, 16 Revisions
EU GMP
Orange Guide
Chapter
changes; 3, 5, 8
ISO 14644‐1&2ISO 14698Revisions
Control Strategy for
sterile’s manufactureHolistic EM, Trend
metrics, no averagingMeasurements:
5 Micron & UDF
Process Simulation;
Alternative media Position of final
sterilising filter RMM – Real time
micro cfu vs bio‐counts
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PHSS Bio‐contamination monograph 20
7
Bio-contamination monograph now published in hard copy and e-book.
The monograph e-copies are free downloads to PHSS members.
R3 Nordic-PHSS Bio-contamination workshop event in Denmark 29 October.
The PHSS are now publishing more on-line GMP regulation change impact statements to support members.
The Risk Management of Contamination (RMC) guidance is under review for update and publication as a PHSS monograph.
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8
New PHSS guidance:
Worked examples of Risk assessments for EM sample location selection and risk based EM
sampling plan/programs.
Risk based Environmental Contamination Control to follow.
PHSS Bio-contamination Special Interest Group (SIG)
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9
Andrew Hopkins, MHRA/ Head of EMA Annex 1 revision group.
Ian Symonds, GSK head of Global Aseptic manufacturing Quality – GSK Barnard Castle UK.
Mike Davies, GSK Global quality auditor, GSK Worthing UK QA Director.
Di Morris, Ex‐MHRA, GSK Compliance auditor manager. PHSS management team member.
Una Hearty, Pfizer Grange Castle, Global Quality.
Benoit Ramond, Sanofi France Global Quality, Microbiology
Tim Eaton, Astra Zeneca, Macclesfield, Sterile product manufacturing specialist.
Alan Dillon, Allergan Westport Ireland Filling line project manager.
Seamus Lyons, Amgen Ireland Aseptic processing QA
Tim Sandle, Bio Products Ltd (BPL) Head of microbiology.
Tim Triggs, DOP systems Director, PHSS management team member.
Tim Russel, TSI (RMM) field developer.
David Jones, Rapid Micro Bio‐systems, Director.
John Wallingford, Pharmagraph (EMS systems) Managing Director.
Steven Robbins, NHS (National health service) Blood transfusion service.
Carl McDonald, NHSBT, Head of bacteriology.
Adam Bird, Oxford Biomedica (Biotech), Head of QA.
Tim Sizer, HNS Regional Quality Pharmacist.
Mark Oldcorne, All of Wales Quality Pharmacist.
Adulmajeed Raji, Porton Biopharma, Microbiologist
Patrick Nieuwenhuizen, Genzyme Ireland Manager Quality Control Microbiology
Corinna Maier, F Ziel GmbH Aseptic processing technologies microbiologist.
Jenni Tranter, Business development manager Synergy Health
Kay O’Hagan, Hospira Quality auditor/ QP.
Wenzel Novak, Groninger GmbH Director of research and development
Michael Pratz Head of Bausch & Stroebel Compliance/ training academy
Johannes Rauschnabel GMBH Bosch packaging GMP expert.
Marc Van Laere Mithra Belgium QA Manager,
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12
Annex 1 Discussion panel
QUESTIONS
PHSS QP UCL Annual Conference
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Introductions to Discussion panel
13
PHSS Moderator: Kay O’Hagan: Senior Qualified person, Hospira UK.
MHRA, EMA: Andrew Hopkins: Senior GMP MHRA Inspector, Head of EMA Annex 1 revision working group.
PDA Worldwide: Richard M. Johnson, President & CEO, microbiologist.PDA UK Chapter President: Dr Siegfried Schmitt Principal Consultant PAREXEL international
PHSS: Di Morris: GSK Compliance Audit Manager, Compliance Audit Group (CAG), Quality Systems and Compliance. PHSS Management team member.PHSS: James Drinkwater: F Ziel GmbH, Head of Aseptic processing Technologies & GMP compliance. Chairman of PHSS.
ISPE/ ISO: Gordon Farquharson: Chair BSI LBI030, Chair CEN TC243, Convenor ISO TC209 wg1, and member ISPE Sterile and HVAC CoP. Consultant Critical Systems.
A3P France: Dr Roland Guinet, Ex AFFSAPS GMP Inspector, WHO GMP auditor, GMP Consultant, University Professor of Microbiology, Head of A3P Annex 1 Interest group.
R3 Nordic: Berit Reinmüller, PhD, Associate Professor in Safety Ventilation, Chalmers University of Technology, Gothenburg, Sweden, R3 Nordic journal editor.
ECA (European Compliance Academy): Dr Jean-Denis Mallet, NNE Pharmaplan, Senior Technology Partner, GMP Expertise, QP, Pharmacist. Head of ECA annex 1 comment working group.
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Annex 1 revision Discussion panel Questions
14
General Concept/ Principles questions
Question 1
The Annex 1 revision concept paper considered the revision may cover Sterile and Non-Sterile product manufacturing.
How does the panel think guidance can be differentiated?
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Annex 1 revision Discussion panel Questions
15
General Concept/ Principles questions
Question 2
The PHSS Bio-contamination special interest group prepared a White paper on Control strategy for manufacture of sterile products and drug substances.
Does the panel believe the requirements for a Control strategy for Sterile products should be included in the Annex 1 revision?
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Annex 1 revision Discussion panel Questions
16
General Concept/ Principles questions
Question 3
Considering data trends are a key performance indicators what trend metrics would the panel consider should be covered in Annex 1 revision?
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Annex 1 revision Discussion panel Questions
17
General Concept/ Principles questions
Question 4
Should Annex 1 include more detailed guidance on Aseptic processing with the increase of aseptic processing used in manufacture of biological products that cannot be terminally sterilised?
Considering the FDA guidance to Industry provides specific guidance on Aseptic processing and currently there are just a few paragraphs in Annex 1 on Aseptic preparations.
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Annex 1 revision Discussion panel Questions
18
General Concept/ Principles questions
Question 5
Concerning the various non-injectable sterile pharmaceutical dosage forms, does the panel consider Annex 1 revision should contain more precise details or dedicated paragraphs?
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Annex 1 revision Discussion panel Questions
19
Question 6 - specifics
Often firms/ end users implement minimum requirements for environmental control, followed by inadequate design layout. Should Annex 1 reinforce the risk based approach over minimum requirements or replace minimum requirements with more specifics?
For example; different processes and barrier technology combinations require different background environments.
Should Annex 1 define when a Grade D (the current minimum) is not considered a suitable background when using Isolator barrier technology in ‘Open system’ Aseptic processing/ manufacturing as defined in the PHSS Bio-contamination monograph 20?
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Annex 1 revision Discussion panel Questions
20
Question 7 - specifics
New technologies including Rapid Micro Methods (RMM) are to be considered in the revision of Annex 1. How can conventional microbiological ‘Not to exceed’ CFU levels detailed in Annex 1 be reconciled with fluorescent based Bio-count levels for GMP compliance?
PHSS comment: It is unlikely there will be widespread adoption of RMM-RT (Real time) methods in Grade A filling zones where environmental data is considered in Batch records and higher recoveries reported as ‘Bio-counts’ will be difficult data to manage without an Annex 1 reference or guidance on correlation with CFUs.
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Annex 1 revision Discussion panel Questions
21
Question 8 – specifics
In an aseptic processing area what is the expectation for grade A continuity for product contacting parts, components and their primary packaging that are sterilised out of place and then subsequently transferred for aseptic assembly.
Is there an expectation that this can be provided by double wrapping parts or is the use of UDF grade A supply transfer carts recommended?
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Annex 1 revision Discussion panel Questions
22
Question 9 – specifics
Is it expected to review in detail the way Annex 1 is written for years to prevent misinterpretation of some statements?
An example is the following: current paragraph 50 contains a sentence that states:
“Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture”.
Interpreting this statement a company (or several companies?) considered that it was acceptable to install a Grade B washing room that was not an aseptic manufacturing area but adjacent to a filling suite with direct operator access, therefore, the washing room was constructed with a drain and operators go in and out the washing room and the filling room during production operations?
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Annex 1 revision Discussion panel Questions
23
Question 10 - specifics
With the increased complexity and diversity of aseptic formulations, the classic use of nutrient media to replace the formulation for process simulation trials (PSTs) is not always feasible, or scientifically justifiable.
Alternative approaches based on risk assessment and scientific rationale could be regarded as equivalent to ensure an acceptable level of aseptic assurance. Is this approach consistent with the intent of the revised Annex 1 document?
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Annex 1 revision Discussion panel Questions
24
Question 11 – specifics
Concerning the MAL (Material Airlocks) can it be considered that a “two door” MAL would be sufficient from Grade D to Grade B material transfers providing it is separated with a “line” in the middle and provided the D operators will never cross that line and additionally the B operators will also not cross the same line from the other side?
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Annex 1 revision Discussion panel Questions
25
Question 12 – specifics
When using gamma irradiated single use systems with integrated point of fill filtration is pre use integrity testing appropriate for this set up?
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Annex 1 revision Discussion panel Questions
26
Question 13 – specifics
When factoring a facility upgrade, in terms of dispensary operations is there a regulatory move for these to be carried out as a minimum within a Grade C environment?
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Annex 1 revision Discussion panel Questions
27
Thank you
The Q&A will be documented and published on the PHSS Website for download
and
shared with our collaboration partnersfor sharing with their association members.
The PHSS will follow the progress of Annex 1 revision to remain engaged with this important development and
advancement
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Revision of Annex 1 Manufacture of sterile medicinal products – a GMP inspector’s point of view.
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Annex 1
Scope•History and Background•Process of revision•Current Status•Why update•Summary
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Annex 1
History and Background•The original version was revised in 1996, 2003, 2005, 2007 and 2009 however there has not been a complete review of the document since it was originally issued• Since the original issuance and the revisions there have been changes in technologies and significant changes in GMP consequent to the adoption of the ICH Q9 and Q10 guidelines.
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Annex 1
History and Background•In 2012 The German Authorities (ZLG) issued a concept statement to the EMA’s IWG proposing revision of the Annex and a subsequent request was made to PIC/S for support in updating•2014 PIC/S Working group was set up and started work in August.•September 2014 a draft concept paper was re- issued to IWG (by the MHRA) supporting the update.
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Annex 1
Process of revision•Combined working group (PIC/S and EMA) with a task of assessing the requirements of revision:
– Update of Question and answer document– Revision of the Annex– Complete re-write
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Annex 1
Process of revision•Combined working group with a task of assessing the requirements of revision:
– Understand Industry concerns– Understand Regulatory concerns
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Annex 1
Process of revision•Draft Concept paper proposed at EMA IWG September 2014•Following regulatory comments and PIC/S input issued for public consultation on 5th February 2015•Deadline for comments was 31st March 2015
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Annex 1
Current Status•Joint working group agreed a new structure•Joint working group commenced work on revision process of content.•Sub groups concentrating on specific areas•Proposing new timelines
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Annex 1
Why update •New Issues
– QRM– Monograph on WFI– Biofilm
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Annex 1
Why update - General opinions•Better clarification
– EM how often (especially lower grade areas)– What does “Grade A Air supply” mean
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Annex 1
Why update - General opinions•Ambiguities?
– Microbiological limits “these are average values”– Freeze Drying Para 34 (Grade A or in sealed
trays under B) conflicts with para 116 (A at all times
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Annex 1
Why update - General opinionsGeneral points for discussion•ISO 14644 5.0µm or not?•Closed systems •Small batch product such as ATMPS•Facility
– Isolators?– RABS ?
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Annex 1
Why update - General opinionsGeneral points for discussion
•Filter integrity testing pre use post sterilisation•Scope – Also applicable to Non sterile manufacturing?•Bioburden sampling
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14
Annex 1
Why update - my opinion(what is the target audience?)
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Annex 1
Why update My opinions•People still don’t understand so need more guidance•QRM ?
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Annex 1
Why update •Losing technical skill level•New and emerging countries where the knowledge has not yet evolved (learning by deficiencies)•New and emerging technologies•Areas not covered
– Media fills, small batches, APIs Campaigns?– New BFS technology– Closed systems
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17
Annex 1
Why update - my opinion(technical knowledge)
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18
Annex 1
Why update - my opinion(process design)
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Annex 1
Why update - My opinions
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Annex 1
Why update - My opinions
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Annex 1
Summary• There are lots of reasons why Annex 1 needs
updating • It is happening• It is a shared project between PICS and EMA
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23
Copyright
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MHRA, EMA: Andrew Hopkins: Senior GMP Inspector Medicines and Healthcare products Regulatory Agency (MHRA), Head of EMA Annex 1 revision working group.
PDA Worldwide: Richard M. Johnson, President & CEO
PDA UK Chapter: Dr Siegfried Schmitt Principal Consultant PAREXEL International
PHSS: Di Morris: GSK Audit Manager, Compliance Audit Group (CAG), Quality Systems and Compliance. PHSS Management team member.
PHSS: James Drinkwater: F Ziel GmbH, Head of Aseptic processing Technologies & GMP compliance. Chairman of PHSS.
ISPE/ ISO: Gordon Farquharson: Chair BSI LBI030, Chair CEN TC243, Convenor ISO TC209 wg1, and member ISPE Sterile and HVAC CoP.
A3P France: Dr Roland Guinet, Ex AFFSAPS GMP Inspector, GMP Consultant.
R3 Nordic: Berit Reinmüller, PhD, Assoc Professor in Safety Ventilation, Chalmers University of Technology, R3 Nordic journal editor. ECA (European Compliance Academy): Dr Jean-Denis Mallet, Senior Technology Partner, GMP Expertise, QP, Pharmacist. Head of ECA annex 1 comment working group.
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1
PHSS Annual Members Conference 2015
Di Morris
Data Integrity
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Data Integrity
• Are concerns over data integrity something new?– No
• Is it just an issue for Quality Control– No its all departments in a company
• Is it happening more– No, we are more aware
• Is it always intentional acts– Not always; a lot are due bad GMP practices
2
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Definitions – Data Integrity
3
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Data Integrity
• It is all in the GMPs for EU, USA and WHO– Chapter 4– Annex 11– 21CFR211 and Part 11
• Examples– Records include the raw data which is used to generate other records. For
electronic records regulated users should define which data are to be used as
raw data. (Eudralex Vol 4 Ch 4)
– Based on the complexity and reliability of computer systems there must be
procedural controls and technologies to ensure the accuracy and security of
computer systems, electronic records and data. Computer systems
must have
adequate controls to prevent unauthorized access or changes to data,
inadvertent erasures, or loss.(21CFR Part 211.68)
4
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Definitions – Data Integrity
The Quality, Safety and Efficacy
of the medicines we make is
assured by applying the regulations and best practice
If we don’t......
Would you be happy taking those medicines
5
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Definitions – Data Integrity
• ALCOA– Attributable– Legible/Permanent
– Contemporaneous
– Original– Accurate
• ALCOA+– Complete
– Consistent– Enduring– Available
Ref MHRA Symposium Dec 2014 and has been used by FDA for many years
This applies to both Paper
and Electronic Systems
The following are examples 6
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Data Integrity ‐
Attributable
Paper Record
• Initials• Hand written signature
They have to be equivalent.
Electronic Record
• Log‐on User identification
• Electronic signature
7
Traceable to a UNIQUE person
You should be able to tell who created, modified, or deleted a record. AND, you can judge if that person was appropriately authorized to do it!
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Data Integrity ‐
Legible
Paper Record• Legible
• No Pencil
• No Correction Fluid
• Permanent Ink
• Correct Amendment of an Error
• Appropriate Archival
Electronic Record• No data annotation tools enabled
• No Over Writing
• No Deletions
• No Hidden Fields
• Changes captured in Audit Trail
• Back‐up and Archive
• Enforced Saving
8
Readable, Traceable Changes, Permanent
You should be able to read all the entries on the paper record. If a change was made, the original value was crossed out with a single line, and the change was dated and initialled.You should be able to see in an electronic files data changes and deletions. Is it clear what the original value was? When it was created and who created it?
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Data Integrity ‐
Contemporaneous
Paper Record• No back‐
dating
• No pre‐completion of a record
• Record the date (and time) of the
activity
Electronic Record• Records saved immediately the
data is entered
• Synchronised clocks
• Locked date and time stamps
9
For a paper record the creation, modification, and deletion of data happens at the right time in the process.For an electronic record when it was created in a process, the audit trail should confirm that.
Record the activity at the time it occurred
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Data Integrity ‐
Original
Paper Record
• Original Document –
Manufacturing record;
laboratory record;
Electronic Record
• Original electronic file
including metadata – a UV
spectra, FTIR spectra
10
The first record made by the appropriate person
if not original should be exact copy - Original records and true copies must preserve the integrity (accuracy, completeness, content and meaning) of the record. Exact (true) copies of original records may be retained in place of the original record (e.g. scan of a paper record), provided that a documented system is in place to verify and record the integrity of the copy. You must be able to reconstruct the activity from the data
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Data Integrity – Certified Copy
• A certified copy is:– Verified by a second person– Compares the copy to the original
– Confirms the copy is accurate and complete
– Documents the verification
– Stamped a ‘true copy’
• What is not a certified copy– A pdf or printout – these are flat files of for example
• A FTIR spectra• A HPLC chromatogram
– They do not preserve the content and meaning
11
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Data Integrity ‐
Accurate
• Accurate, consistent and real representation of facts.
• No editing without documented amendments /audit trail
entries by authorised personnel– Make sure of the information that you are recording is correct,
honest and transparent
– Record the data directly into the controlled unique blank record/bound book/electronic programme
– Where possible use automatic data capture
– Are the electronic record the same as the paper record
12
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Data Integrity – ALCOA+
• Complete– All data from an analysis, from the start of analysis to the end
and any
repeated or reanalysis performed on the sample.
– For electronic systems, the paper output must be linked to the
underlying electronic records used to produce it.
• Consistent– All elements of the analysis, such as the sequence of events, follow on
and data files are date (all processes) and time (when using electronic
systems) stamped in the expected order
• Enduring– Recorded on authorised media e.g. laboratory notebooks, numbered
worksheets, for which there is accountability or electronic media
• Available– The complete collection of records can be accessed or retrieved for
review over the lifetime of the record.13
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Data Integrity – Data Governance
14
• MHRA Definition:• The sum total of arrangements to ensure that data, irrespective of the format
in which it is generated, is recorded, processed, retained and used to ensure a
complete, consistent and accurate record throughout the data lifecycle.
– It should be integral part of the Pharmaceutical Quality System
– There should be clear Management Responsibilities
IT should be part of Management Reviews/Quality Councils
Everyone should be trained to understand the terms and implications of IT
systems
—
There should be data owners such as process owners in computer
systems
—
There has to be data integrity training
—
There has to be procedures and processes in place
—
Create a blame free, open and transparent culture
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Data Integrity – Data Definitions
Record Observation Hybrid Electronic
Raw Data
Written record
Electronic files of the
analysis
Electronic files of the
analysis
Metadata
Further written data about
the sample and analysis e.g.
batch, test, analyst, date,
etc.
Electronic Files for control
of the instrument, data
acquisition, interpretation
and reporting of data.
Identification of who tested
the sample, etc.
Audit trail entries of data
changes
Further written data about
the sample and analysis e.g.
batch, test, etc.
Electronic Files for control
of the instrument, data
acquisition, interpretation
and reporting of data.
Identification of who tested
the sample, etc.
Audit trail entries of data
changes
Further written data about
the sample and analysis e.g.
batch, test, etc.
Review
Reportable result
Handwritten signatures of
tester and reviewer
Printout of reportable result
Handwritten signatures of
tester and reviewer
Linkage to underlying
instrument raw data and
spreadsheet file
Reportable Result
Electronic signatures of
tester and reviewer
Linkage to all data and
metadata via application
database
15
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Data Integrity ‐
Impact
16
• Access to raw data for staff performing data checking
activities (MHRA)
– This is similar to the FDA GMP requirement for complete
data and for the second person review to see all data
generated in the course of an analysis.
– This means a review of the source data eg electronic HPLC
data
What about QPs certifying for release batches not made on site?
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Data Integrity
• The MHRA guidance (v1.0) stated that organizations are “not
expected to implement a forensic approach to data checking,
….”.
However the revised version now reads “not expected to
implement a forensic approach to data checking on a routine
basis, ….”
• QPs must ensure systems, procedures, training, culture and
management responsibilities for data integrity are clearly in
place and they have time to do this on all their suppliers to be
able to certify batches
17
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Data Integrity ‐
Consequences
• So what does this mean:– What happens when data integrity is breached? The worst
case scenario is impact on patient safety and the loss of lives.
– the recent New England Compounding Pharmacy incident
in the United States can be used as an example of the
consequences of fraudulent activity. Here, 64 patients
died and over 750 were sickened from fungal meningitis as
a result of sterility negligence and data integrity issues. In
this case, a FDA official said pharmacy technicians were
instructed to lie on cleaning logs, showing rooms as being
properly cleaned when they had not been
18
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Data Integrity ‐
Consequences
– we have to embed ALCOA+ principles into our ways of working
across the WHOLE
of the business –
Development to
commercial manufacturing
– Data generated in development impacts the Quality attributes
in commercial manufacture – the data has to be trusted
to be
complete and accurate
– Stability data supports product in the market any data integrity
concerns impact the product and may result in recall
– Data Integrity issues can result in loss licence, recalls, loss of jobs and patients not having their medicines
19
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Data Integrity – Recent Issues
• pH meters and balance printers:– Date and time not locked
– Evidence of data being changed and reprinted– Undated records found in a bin
• Batch record had pre‐populated sections
• Validation protocol had typed in results that had been signed
and dated ‘on the day of the test’
• Reprints of worksheets not tracked and reconciled
20
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Data Integrity – Recent Issues
• Failure to record activities at the time they are performed and
destruction of original records
• Batch records were completed after the operations had
ended
• Failed to maintain original manufacturing data for critical
steps – had uncontrolled loose paper, unbound, rough notes,
transcribed and then originals destroyed
• Back dated batch records
• Laboratory equipment lacked controls to prevent raw data
from being deleted or altered.
21
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Data Integrity ‐
HPLCs
How do the
Part 11 regulations and "predicate rule requirements" (in 21 CFR
Part 211)
apply to the electronic records created by computerized
laboratory systems
and the
associated printed chromatograms that are used in drug manufacturing and testing?Some in industry misinterpret the following text from “The Guidance for Industry – Part 11,
Electronic Records; Electronic Signatures – Scope and Application”
(Part 11 Guidance; lines 164
to 171) to mean that in all cases paper printouts of electronic records satisfy predicate rule
requirements in 21 CFR Part 211.The printed paper copy of the chromatogram would not be considered a “true copy”
of the entire electronic raw data used to create that chromatogram, as required by 21
CFR 211.180(d). The printed chromatogram would also not be considered an “exact
and complete”
copy of the electronic raw data used to create the chromatogram, as
required by 21 CFR 211.68. The chromatogram does not generally include, for
example, the injection sequence, instrument method, integration method, or the
audit trail, of which all were used to create the chromatogram or are associated with
its validity. Therefore, the printed chromatograms used in drug manufacturing and
testing do not satisfy the predicate rule requirements in 21 CFR
Part 211. The
electronic records created by the computerized laboratory systems must be
maintained under these requirements.
Date: 8/3/2010 22
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Data Integrity ‐
HPLCs
Why do HPLCs attract so much attention?
•Because we don’t use them as they are meant to be used
•We treat them as we did with ‘integrators’
•We should not be running unintegrated chromatograms and
then putting in the processing parameters
•We should be:– Second person checking the sample sequence then locking it
– We should be locking the method and ALL processing parameters
– We should be using the system to generate the data at time of
analysis
– We should be giving sufficient time for the column to equilibrate and
not use ‘trial’
injections
•We should not be manually manipulating certain
chromatograms (assay, dissolution) 23
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Data Integrity ‐
Issues
• The computer system access rights
– The system administrator worked in the laboratory
– The administrator must be independent of the department
– The independent department must have appropriate
procedures and controls
– The analyst/operator had the access to modify the
method/recipe
– How to modify was clearly documented in the equipment use
procedure
– Only the administrators procedures should have that level of
detail
24
Distribution rights are property of the PHSS, permission must be obtained for use.
Data Integrity ‐
Issues
• The HPLC system did not have proper controls in place to prevent
unauthorised manipulation of the laboratories raw electronic data.
• The HPLC systems did not have access controls to prevent
alteration or deletion of data
• The HPLC software lacked an audit trail recording any changes to
the data, including previous entries, who made changes and when
the changes were made
• The laboratory and manufacturing personnel shared common log‐
ins and passwords to access the system
• The Quality Unit was unable to retrieve the original raw electronic
data because the back‐up discs were unreadable/over written
25
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Data Integrity ‐
Conclusion
• The message for data integrity is clear.
• It’s not a new concept; it’s about getting back to the roots of training all
staff on the importance of data integrity in cGMP documentation and
honesty.
• It is critical to ensure employees understand the accountability
and
traceability requirements for retention of raw data and the consequences
of data manipulation.
• Training operators and analysts to document the performance of a task by
recording what happened at the time it occurs, including information
about the person who performed it along with clearly documenting
and
investigating deviations, is vital for patient safety and product efficacy.
• This is achievable by providing the training and creating a company
culture that promotes and rewards ethical behaviour as a core value from
top to bottom of an organization.
26
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Data Integrity
Thank you
27
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Changes in EU GMP / MHRA Orange Guide chapters 3, 5, 8 and annex 15
1Malcolm Holmes ‐
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conference
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Chapter 3:
Premises and
Equipment
Chapter 5:
Production
Chapter 8:
Complaints,
Quality Defects
and Product
Recalls
Annex 15:
Qualification and
Validation
2Malcolm Holmes ‐
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conference
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Changes Chapters 3 & 5
Chapter 3 Chapter 5
Malcolm Holmes ‐
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With transitional arrangement for toxicological evaluation
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Additional Changes Ch 5
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Section
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Background Need For Dedicated Facilities
5Malcolm Holmes ‐
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conference
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Why
6Malcolm Holmes ‐
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conference
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Potential Impact
7Malcolm Holmes ‐
PHSS 2015 members
conference
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Dedicated Facilities
Regulator positioning ?
• Its a highly potent product
of a type which would
previously have been
manufactured in dedicated
facilities. Therefore that
would appear to be a good
starting point.
Manufacturer positioning ?
• Its a highly potent product
of a type which would
previously have been
manufactured in dedicated
facilities. I want you
“techies”
to find me a way
to safely manufacture it in
shared facilities.
Malcolm Holmes ‐
PHSS 2015 members
conference8
All parties must be very careful not to manipulate their risk
management decisions to facilitate their pre‐determined
desired outcome
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CH 5 – Reporting Product Shortage Due To Manufacturing Constraints
Malcolm Holmes ‐
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conference9
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Ch 5 Testing Of Starting Materials
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conference10
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Ch 5 Rationale For Outsourcing Of Testing
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conference11
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Ch 8 ‐
Complaints, Quality Defects and Product Recalls
Malcolm Holmes ‐
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conference12
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Annex 15: Qualification And Validation
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conference13
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Annex 15: Some Significant Changes
Malcolm Holmes ‐
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conference14
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Validation – A State Of Mind
15Malcolm Holmes ‐
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conference
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Summary
Basics
• In general more detail is
given. New versions
substantially longer than
previous versions
• All based on significant
modernisation of GMP
thinking ‐
ICH Q8, Q9 &
Q10 – Particularly ICH Q9
(Quality Risk Management)
Remember ICH Q9 key principles
Malcolm Holmes ‐
PHSS 2015 members
conference16
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Culture
Kim Sandell ‐
Pfizer
17Malcolm Holmes ‐
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Communication MHRA & Industry
Malcolm Holmes ‐
PHSS 2015 members
conference18
Over last 12 months or so MHRA through
its Innovation Office has published
convincing summaries of how it has been
able to help Industry make appropriate
choices in design of facility/ process /
product.
This is good risk management by both
MHRA and Industry which leads to better
patient safety.
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Workshop
Malcolm Holmes ‐
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conference19
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1
PHSS Annual Members Conference in association with UCL Q3P 2015
Richard Funnell
FunnellPharma
ConsultantsLtd
Annex 16:What is changing?
What are the implications?When is it going to happen?
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Annex 16: Introduction
•
Work on revision started 4 years ago!
•
Still not issued.
•
Most recent public draft has moved on.
•
Annex 16 rebuilt and designed to:
–
Reflect increasing supply chain complexity.
–
Include new legislation.–
IMP legislation
–
Falsified Medicines Directive
–
2009 reflection paper on unexpected deviations
–
Increase consistency across the EEA.2
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Annex 16: Introduction
•
We will:
–
Pick out eleven key points.
–
Examine the controversial areas.
–
See what the practical implications may be.
–
Have some discussion.
3
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Access to MA
• 3.3. “…
it is expected that the QP has access to the necessary details of the MA…”
Hopefully obvious but now formal. Should help
the QP.
4
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Shared responsibility
• 3.3. “…responsibility may be shared with other QPs who have confirmed compliance of specified steps in
the manufacture and control of a batch…”
Reflects increased manufacturing across different companies.
Previously implicit?
Legal implications?
5
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“Virtual”
importers
• 3.4.2. “Importation activities including at least receiving, sampling, storage of the unreleased and
uncertified batch, QC testing, certification and release should be conducted by authorised sites…”
What does “authorised”
mean?
UK currently allows physical receipt at WDA holder (with conditions).
CONTROVERSIAL.
Still not agreed!
6
Distribution rights are property of the PHSS, permission must be obtained for use.
Imported batches –
location of sampling
• 3.4.6. “Samples of imported product should in full be representative of the batch and therefore, be taken
after arrival in the EEA...”
REMAINS CONTROVERSIAL
A 50/50 split across member states:– 50% accept samples being taken at manufacturing site
– 50% require at least some samples to be taken after arrival in EU.
7
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Location of sampling continued
• A further iteration allowed reliance on samples taken at manufacturing sites but with certain conditions. For
example:• Need a formal risk assessment and study to justify samples
representative (e.g. comparative analysis of samples taken in
both places).
• Review time between sampling and eventual shipment to EU.
• “Random periodic analysis of samples taken after importation...”
Reflects industry desire?
8
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Location of sampling continued
• 3.4.8. Covers further importation of the same bulk batch.
– Subsequent imported amounts should be subject to ID and assay
within EU.
– Storage and transportation “similar”
on each occasion.
– Samples originally tested should be representative of all
subsequent
batches.
ALSO REMAINS CONTROVERSIAL – PUSH TO RETAIN STATUS QUO
9
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Allowable QP delegation:
• 3.5. onwards ‐
a short list of what QP must do personally.
• 3.5.4. onwards ‐
a longer list of what QP is responsible for but may delegate.
Clarifies and reflects QP codes of practice (a UK document).
10
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API responsibilities
• 3.5.5. and 3.5.9. State QP must have supply chain knowledge and responsibility for API GMP and GDP.
– QP should have a documented supply chain available
– QP needs to ensure API manufactured and sourced according to GMP
and GDP.
Now well entrenched. Reflect Falsified Medicines Directive
11
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Parallel importing
• 3.7. A new section on parallel importation and distribution.
– QP should confirm compliance with national requirements and EU
rules on this.
– “The re‐packager should ensure that product …has been obtained
from the authorised supply chain.”
– “Re‐packager must ensure authenticity by verifying safety features
where applicable.”
Much more common than when original Annex
16 was published.
12
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Control reports
• 3.8.2. “The control report … or another proof of certification should be made available … for the batch to be exempted from controls when entering
another member state…”
This is an existing legislative requirement.
Therefore difficult to ignore!
Not widely adhered to?
13
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Audits by third parties:
• Section 4 “Relying on GMP assessments by third parties e.g. audits.”
• Six sub‐points. Quite a bit of detail……..
14
Distribution rights are property of the PHSS, permission must be obtained for use.
Unexpected deviations:
• Section 5: Principle of 2009 reflection paper in Orange Guide but stripped right down.
– API, excipient and FP registered specs no room for manoeuvre–
need
a batch specific variation (in UK).
– The impact of the deviation should be assessed under a quality risk
management process such as described in Part III.
– Evaluate impact on safety, quality and efficacy.
– Consider putting on stability.
15
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Shipment under quarantine:
• 6.1. “Until a batch is released it should remain at the site of manufacture or be shipped under quarantine
to another authorised site.”
“Authorised”?
Some member states allow shipment under quarantine to a WDA holder.
Others would only allow shipment to an MIA holder.
ALSO CONTROVERSIAL
16
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The future:
• Final wording still not agreed.• Don’t know when final version will be issued.• Two areas in particular may change.
• Annex 21.
17
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1
PHSS Annual Members Conference in association with UCL Q3P
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Agenda Review of all the standards in the ISO 14644 family Background to why a revision of part 1 & 2 was required. The status of current ISO 14644-1 & 2. The challenge of improving ISO 14644-1:1999 Timeline for the new standards. ISO 14644-1
New – classification by table. New – number of sample locations. Update to sequential sampling procedure. Handling Ultrafine particles – now in Nano-particle monitoring standard. Keeping the concepts of Macro-particles Test methods update.
Revision of ISO 14644-2 Change to a standard for monitoring only. The monitoring plan. Guidance about critical parameter monitoring.
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ISO TC209 confirms the essential attribute of a cleanroom “Air cleanliness by particle number concentration”
There has been some confusion !!ISO TC209 standards we have several different cleanliness attributes:
Airborne & surface particles
Airborne & surface chemicals
Airborne & surface micro
Question - Should we be able to designate (classify) a cleanroom by any one of the cleanliness attributes?
In October 2014, ISO TC209 clarified the position
A “cleanroom” must be characterised by air cleanliness class by particles. If other attributes are important for a particular industry or process/product, then we can monitor for these in addition.
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13
Very important !!!!!
Status of ISO 14644-1 & 2The information here is for information only.
Not to be used for classification or monitoring of cleanrooms.
EN/ISO 14644-1:1999 & 14644-2:2000 remain the applicable standard for classification by airborne particles !!!!! No change until replaced by the new standards.
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ISO TC209 WG1 Timeline (10 years + in the making!) Target publication December 2015
FDIS enquiry vote August 2015 2nd DIS enquiry PASSED vote in November 2014 1st DIS enquiry vote December 2010 CD vote out October 2009 (This stage delayed due to
challenging discussions) NWIP = WD 2 = CD complete Sept 06 4th WG 1 meeting Beijing 6-8 September 06. 3rd WG 1 meeting June 06 Sweden (SIS Stockholm)
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Simplification: The 95% UCL Evaluation for 2-9 locations has been removed.
Each sampling location now evaluated separately. All must complyfor room or zone to comply.
There is a Look-up table, based on ensuring 95 % level of confidence that at least 90 % of the cleanroom or clean zone will comply with the class limit.
Will increase the number of locations up to 1000m2.For > 1000m2, very similar to the current Area rule.
Placement of sample points: Even distribution, at representativelocations In N-UDF cleanrooms with non-diffused airflow, avoid placement directly under HEPA filter supply
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29September 2015
Required minimum sampling locations
1. Determine the number of sample locations NL from table A1.
2. Distribute the sample locations throughout the cleanroom (or clean air device) at representitive locations (not under undiffused HEPA filter terminals).
3. Take sample at each location (as existing standard)
4. If all measured particle concentrations comply with the class limit, the classification is passed.
5. For larger rooms >1000m2, extrapolate the location density from the 1000m2 requirement.
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Test methods & Instruments
ISO TC 209 has decided that each classification standard needs to have its own test method and test instrument guidance on-board.
Better than in a separate standard.
Makes revision of standards easier to keep coordinated.
Annex F imported from ISO 14644-3 with some updating.
Most important reference is ISO 21501-4:2007.
No direct impact on users.
Makes each standard more complete and easier to use.
ISO 14644-3 will now only deal with the support tests for cleanrooms: Filter leak
Airflow velocity and volume
Pressurisation
ISO 21501-4:2007 describes a calibration and verification method for a light scattering airborne particle counter (LSAPC), which is used to measure the size and particle number concentration of particles suspended in air. The light scattering method described in ISO 21501-4:2007 is based on single particle measurements. The typical size range of particles measured by this method is between 0,1 µm and 10 µm in particle size.
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Tables of frequency removed; guidance retained in text.
Annual classification required, and after modifications, or after monitoring deviation and rectification.
Annual classification is the default minimum monitoring required, but interval can be extended if automated monitoring system provides satisfactory data.
Monitoring should include: Air cleanliness Pressure differential Airflow velocity in UDF Airflow volume in non-UDF.
This change will make it easier to use RISK BASED decision making about testing frequency.
Means if GMPs need to be specific, they can in the context of the ISO guidance.
e.g. In Pharma sector, US FDA’s 6 monthly leak testing of HEPA filters in the aseptic core.
environments with integrated risk based environmental monitoring
systems.
• Cleanroom background environment to Isolator barrier: Grade C for ‘Open processing’
of pharmaceutical products. Filling zone positive pressure to surround.
• Cleanroom HVAC configured for part recirculation and fresh air exchange.• Isolator air‐handling system configured for part recirculation and air exchange (that can
take supply from the surrounding environment and discharge back to the same
environment).
• Secure ‘Closed’
material transfer devices required for all process support materials
(including environmental monitoring).
• RTU: pre‐sterilised containers may enter the Grade A Filling environment via de‐bagger/
No‐Touch‐Transfer (NTT) using a combination of barriers, pressure differential and
aerodynamic protection contamination control measures.
• VHP‐H202 surface decontamination to be used for Isolator barrier, non‐contact machine
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Formulation
VHP
Rapid Decon
VHP MT change
QC
inspec
t
releas
e
Labelling/
packaging final
product QC and
batch release
De‐Bag
NTT.+RABS
Vial
CappingRABS. +
Stoppers
Caps
Tub-nest
SUS/ EM/ Rejects/ waste/ tools
Product
White Cart
Grey Cart
SBI++
Grade C Surround
VHP Rapid Decon Station (RDS) for SUS/ EM/ Cleaning materials: delivery in RTP canisters plus Cross contamination control decontamination (at material exit from process).
Material/ waste VHP Surface Decon In/Out
Example of a process flow diagram showing areas of interaction
with a Pre‐sterilised Syringe Filling process in an Isolator
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19
Aseptic processing with Containment Isolation
Aseptic
processing
Toxic products
New products types requiring Contamination control,
Cross contamination control and Operator protection
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environments with integrated risk based environmental monitoring
systems.
• Cleanroom –
Isolator background environment: Grade C for ‘Open processing’
of
pharmaceutical products. Filling zone positive pressure to surround but less positive than
additional adjacent Isolator Grade A modules to provide a containment measure.
• Cleanroom HVAC configured for part recirculation and fresh air exchange.• Isolator air‐handling system configured for part recirculation and air exchange: Air supply
taken supply from surrounding environment and vent discharge ducted to outside via
double HEPA filtration and Bag‐in/Bag‐Out filters on primary containment boundary.
• Secure ‘Closed’
material transfer devices required for all process support materials
(including environmental monitoring).
• Wash/ Decontamination in‐place systems for primary containment boundary.• RTU: pre‐sterilised containers may enter the Grade A Filling environment via de‐bagger/
No‐Touch‐Transfer device via Isolator modules each side of Fill zone to provide a high
pressure barrier so air flows into grade A Fill zone and into de‐bagger (without mixing).
• Active ‘Mouse’
hole and external vial washer/ Decon
may be required.• VHP‐H202 surface decontamination used for Isolator barrier, non‐contact machine
surfaces, surface sterilisation of stopper bowls/ guides, packaging difficult to manually
disinfect.
Aseptic Filling of Toxic (cytotoxic) productsPrinciple requirements
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Environmental Monitoring (EM) Rapid – Real time Micro MethodsStatus of development and use in GMP/ Aseptic processingRapid – Real Time Environmental monitoring systems are developing and are
increasingly being implemented in Aseptic processing, currently in support areas
(outside grade A) and for root cause investigations
These technologies employ fluorescence based analytical systems that are
‘intervention free’
(no need to position a sample plate) with Real time feed back
in detection/ warning of Bio‐counts that are above alert and action levels hence a
change in the control state.
Conventional microbiological monitoring employs growth based systems with
inherent low recoveries. Not to exceed cfu levels/ limits defined in EU GMP
Annex 1 and FDA Guide to Industry for Aseptic processing are based on cfu’s.
RMM – RT measurements in bio‐counts are more sensitive with higher recovery
(from air samples) and subject to ‘false positives’
as a result of measuring non‐
biological fluorescing molecules e.g. cellulose.
Until EU GMP Annex 1 and PICS (FDA aligned) recognise the difference in cfu
and bio‐counts there will be limited implementation for Grade A/ ISO5
manufacturing areas where the EM data is considered in Batch release/ part of
Batch records.
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32
New PHSS guidance:
Worked examples of Risk assessments for EM sample location selection and risk based EM
sampling plan/programs.
Risk based Environmental Contamination Control to follow.
PHSS Bio‐contamination Special Interest Group (SIG)
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33
Andrew Hopkins, MHRA/ Head of EMA Annex 1 revision group.
Ian Symonds, GSK head of Global Aseptic manufacturing Quality – GSK Barnard Castle UK.
Mike Davies, GSK Global quality auditor, GSK Worthing UK QA Director.
Di Morris, Ex‐MHRA, GSK Compliance auditor manager. PHSS management team member.
Una Hearty, Pfizer Grange Castle, Global Quality.
Benoit Ramond, Sanofi France Global Quality, Microbiology
Tim Eaton, Astra Zeneca, Macclesfield, Sterile product manufacturing specialist.
Alan Dillon, Allergan Westport Ireland Filling line project manager.
Seamus Lyons, Amgen Ireland Aseptic processing QA
Tim Sandle, Bio Products Ltd (BPL) Head of microbiology.
Tim Triggs, DOP systems Director, PHSS management team member.
Tim Russel, TSI (RMM) field developer.
David Jones, Rapid Micro Bio‐systems, Director.
John Wallingford, Pharmagraph (EMS systems) Managing Director.
Steven Robbins, NHS (National health service) Blood transfusion service.
Carl McDonald, NHSBT, Head of bacteriology.
Adam Bird, Oxford Biomedica (Biotech), Head of QA.
Tim Sizer, HNS Regional Quality Pharmacist.
Mark Oldcorne, All of Wales Quality Pharmacist.
Adulmajeed Raji, Porton Biopharma, Microbiologist
Patrick Nieuwenhuizen, Genzyme Ireland Manager Quality Control Microbiology
Corinna Maier, F Ziel GmbH Aseptic processing technologies microbiologist.
Jenni Tranter, Business development manager Synergy Health
Kay O’Hagan, Hospira Quality auditor/ QP.
Wenzel Novak, Groninger GmbH Director of research and development
Michael Pratz Head of Bausch & Stroebel Compliance/ training academy
Johannes Rauschnabel GMBH Bosch packaging GMP expert.
Marc Van Laere Mithra Belgium QA Manager,
Distribution rights are property of the PHSS, permission must be obtained for use.
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James L Drinkwater F Ziel
Head of Aseptic processing Technologies & GMP Compliance
Risk Based process solutions in Environmental Control and Monitoring for
Aseptic processing and Filling
Distribution rights are property of the PHSS, permission must be obtained for use.
over 25 years of advancing pharmaceutical and healthcare sciences
PHSS Annual Conference in association with UCL Q3P