9. The RP’s Duties and GDP Inspectionsinglasia.com/.../02/...Duties-and-GDP-Inspections1.pdf · The RP’s Duties and GDP Inspections Hilton Olympia, London 12th February 2013 ...

9. The RP’s Duties and GDP Inspections

Hilton Olympia, London 12th February 2013

© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012

Calcott Consulting consultant to the pharmaceutical & biotechnology industry

Presenter’s note

• Please note, the slides contained herein, along with the narrative, are of a generic nature. These have been created in order to promote the general understanding of the principles of EU Good Distribution Practice for Medicinal Products.

• The author and presenter does not accept any liability for any inappropriate action taken or misinterpretation of legislation.

© Copyright inglasia pharma solutions Ltd /

Calcott Consulting LLC. 2012

LEARNING OBJECTIVES

• What are the Roles and Responsibilities of the Responsible Person or Qualified Person in The Distribution of Medicinal Products?

• The Regulatory Authority Inspection

• What would the Inspectors Expect to See?


Presenter

Presentation Notes

The Responsible Person plays a very important role in ensuring the holder of the WDL complies with medicinal product legislations and Guidelines for the provisions of GDP. This presentation will address these responsibilities and also the kind of experience someone would require to be eligible to act as an RP. We will also be looking at regulatory authority inspections and how these are generally conducted and what they tend to look at during the inspection. Also what are the hot topics that regulators pick on in an inspection. The RP has to always be present in the GDP regulatory authority inspection so this would be a good subject to address in this presentation as we will be discussing the responsibilities of the RP.

What Are The Main Responsibilities of the RP/QP in

Distribution?

• Safeguarding against potential hazards

• Ensure wholesale dealer’s licence conditions are met

• Ensure compliance to Good Distribution Practice


Presenter

Presentation Notes

The RP/QP is responsible for safeguarding product users against potential hazards arising from poor distribution practices. They ensure that the conditions of the wholesale dealer’s licence are met. The RP/QP ensures that the guidelines of Good Distribution Practice are complied with. They must be contactable at all times for example, in the event of a recall!

Qualification of The Responsible

Person


• Education – Pharmacy Degree or suitable qualification

• Working Experience – Competency, knowledge and on going GDP training

• Audits – Performed internal and externals

audits

Presenter

Presentation Notes

Education: In the majority of EU member states and in South Africa, the Responsible Person (for the provisions of GDP) is called the Qualified Person or Responsible Pharmacist. They are qualified pharmacists. In the UK and Ireland they are referred to as the Responsible Person and they do not need to be pharmacists. However UK and Ireland RPs should have a degree in science, such as Chemistry, Microbiology or Biology. In other countries, such as UAE, a designated person should be appointed at each distribution point. The designated person should have a defined authority and responsibility for ensuring that a quality management system is implemented and maintained. This requirement for a designated person at distribution points is also detailed in the WHO GDP Guidelines. In the US, Canada and Australia there is currently no specific requirement for a designated person for the oversight of the QMS. Everyone in the organisation is responsible for compliance with GDP. Working Experience: In the UK and Ireland where the RP is not a pharmacist or eligible to act as a Qualified Person (QP), they should have at least one year’s practical experience in both or either of the following areas: handling, storage and distribution of medicinal products and transactions in or selling or procuring medicinal products. In addition, the RP should have at least one year’s managerial experience in controlling and directing the wholesale distribution of medicinal products; on a scale, and of a kind, appropriate to the licence for which they are nominated. They should also be able to show that they have received on going GDP training or attended training to keep updated on changes in regulations. Performing Audits: We would recommend that anyone wanting to become a Responsible Person gains experience by also performing internal and external audits which would involve looking at Quality Systems, warehouse operations and other contracted services such as transport and destruction. This would give a good understanding on the distribution operations and how each aspect of the goods receiving, storage and despatch connect with one another and where improvements can be made to comply with the regulations and guidelines.

The RP Job Description


• So what areas should typically be addressed in the Job Description as a minimum for the provisions of GDP? Ensure compliance with the general conditions of the authorisation Ensure compliance with the requirements of GDP guidelines Ensure that all aspects of the quality system are implemented and

maintained Involved in the approval of controlled documents Involved in self inspections Ensure that all relevant staff members are trained in the duties assigned to

them Review temperature records on a regular defined basis Approve for return to saleable stock any medicinal product returned by a

customer. Involved in any decision to quarantine or dispose of returned, rejected,

recalled or counterfeit products Approval of contracted services and their ongoing evaluation Involved in the approval of suppliers and customers To fulfil their responsibilities personally.

Presenter

Presentation Notes

The RP should know the additional requirements now included in the new EU GDP Guidelines and be able to assess the current controls applied in the company and what additional work needs to be performed, if any, to comply with the new guidelines. It would be extremely beneficial for the RP to utilise risk assessment tools to be able to categorise and priorities any improvements to processes and procedures. In addition, the RP having knowledge of the falsified medicines directive (FMD) 2011/62/EU would be advantages as this would help in knowing the legal requirements for why the EU GDP guidelines needed to be revised. It also provides more details on the RP duties through out the supply chain fro sourcing of raw materials to supplying finish product to customers.

The RP Should Have…


• a clear reporting line to the license holder or Managing Director;

• personal knowledge of the products traded under the license and the conditions necessary for their safe storage and distribution;

• access to all areas, sites, stores and records which relate to the licensable activities and regularly review and monitor all such areas, etc. and the standards achieved

• Experience with hosting or being involved in regulatory authority inspections

Presenter

Presentation Notes

The RP should have the authority to inform the company Managing Director of any incidences that impact on patient safety or are likely to cause a risk to patient safety. This would also apply to a contract RP however the company must have in place a Quality Agreement with the RP before utilising their services. Contract RPs should be considered as permanent employees and they should be trained on company procedures and processes before they can undertake their responsibilities. Their training to be documented in their training file. The Quality Agreement (QA) with a contract RP should address the requirements detailed in a permanent RPs job description. So the points addressed on the previous slide should be included in the QA.

Affiliate Office RP (MA Holder in that Country)


• Procure and sell medicinal products; • Outsource warehousing and storage to

outside business partner; • Outsource any rework of product (secondary

packaging/labelling) to outside business partner;

• Outsource despatch of product to outside courier service.

Presenter

Presentation Notes

The duties of the RP at the Affiliate office are not as extensive as the duties of an RP at the warehouse as many of the services involving the handling of product are outsourced. However the affiliate is involved in certain operations which are subject to adherence to the GDP Guidelines. In majority of the countries in Europe, if your premises performs procuring and selling of licenced or unlicensed medicinal products then your premises should hold a wholesale dealer licence, issued by your competent authority. It is very likely that you will also be inspected by your competent authority. If you are unsure you will need to check with your competent authority of whether you will need a licence for the operations your perform at your office. Typically the RP duties at the Affiliate would involve oversight of procurement, sales order processing, bona-fide checks, inventory control, returns and destruction which is normally performed by the customer services department. The RP should evaluate contract service providers such as warehouses and courier services and implement and maintain Quality Agreements with these providers. Also review and approval of procedures, managing customer complaints, recalls and training, self-inspection and audits for the provisions of GDP. Further details on this will be provided in the QMS session on day 2.

GDP Inspections - what to

expect before, during and after • The inspector will:

– Assess compliance with the principles and

guidelines of Good Distribution Practice; – Assess compliance with the provisions of the

wholesale dealer’s license; – Conduct ‘for cause’ inspections, as necessary.


Presenter

Presentation Notes

First we have to remember that an inspector is a human being who has good and not so good points. But they are very knowledgeable in the legislation and guidelines and they have got a job to do. They are an individual so each inspector will have a different style of auditing and also their personality will be different from one auditor to another! However they will generally follow a certain method of auditing which we will discuss of the next few slides.

Inspection Process

• Four parts of an inspection:

– Opening Meeting; – Facilities/security/storage areas (if applicable); – Review of records/documentation; – Close-out Meeting


Presenter

Presentation Notes

When the inspector arrives on site they would observe the building and the surrounding to look for anything visual that contravenes the Guidelines for example no security measures on the outside of the building. On entry into the building they would expect to be signed in and issued with a visitor’s pass. They will need to be escorted when on the premises. They will then generally follow the audit in the order of an opening meeting, requesting a company presentation, certain documents ahead of their review and then onto a tour of the facility. On completion of the tour they will start review of documents and interviews of SMEs. They will then conclude, feedback and close audit. We will touch on these over the next few slides.

Opening Meeting

• What the inspector wants from you; • What you can expect of the inspector; • Company background/personnel (who does

what); • Staff/staff training; • Anti-counterfeit awareness/strategy/bona fides

check; • Returns policy and management; • Quality Agreement; • Transportation management; • Recall management.


Presenter

Presentation Notes

When they are settled in the meeting room the opening meeting will commence. When they start requesting documents make sure you are ready to show them everything they want to see on the day on the inspection. What the inspector will see is a snap-shot in time so they will not know what you did the day before or what you will be doing tomorrow. You may receive a deficiency when maybe it is not a justified deficiency so make sure the facts are all readily available at the inspection. They will review your documentation/training, interrogate validated systems, walk about and chat and have interviews with staff at all levels. They are there to enforce Regulatory requirements and they will assess Company Compliance and controls. It will be 50% visual inspection and 50% documentation inspection. The hot topics with inspectors recently have been customer and supplier verifications, quality agreements, returns and controls on transportation and these seem to be more in line with the changes to the EU GDP guidelines which also place new emphasis on these areas.

Site Inspection

• The premises – physical walk around; • Inspection of all storage areas; • Inspection of special storage areas (e.g. returns,

quarantine, disposal); • Pest control/housekeeping; • Stock and stock management; • Goods in (receipt and check-in of deliveries); • Temperature monitoring and recording (location

and suitability of temperature recorders, etc.); • Temperature monitoring equipment/calibration; • Goods out


Presenter

Presentation Notes

We check we are doing everything OK (Follow company SOP on preparation for Regulatory inspection). Perform a mock inspections and train everyone that might be involved. Organise the whole thing and remember the Control Room! And during the rehearsal or training make sure personnel work as a team and not a set of individuals. It’s like a test of the system of which you are a part – revise well. Know the legislation and guidelines/ Where is it? Know your Policies, SOP’s/WIs-/ Where are they? Know what you do and exactly how you do it – if not sure refer to relevant SOP and Wis. Even as the RP Make sure you have been trained/training records are available and of course the job description.

Review of Documents and Deficiencies

• Review of quality system (SOPs); • Review of temperature records; • Review of training records; • Review of purchase and sales documentation; • Review evidence of bona fide checks; • Review any other documentation as required; • Review and categorisation of any deficiencies

found


Presenter

Presentation Notes

During the review of documents by the inspector try and be relaxed as they will be asking you questions as it is a process of gaining information and confidence in you. They will dig to find answers so they will ask for help/demonstrations and also for evidence on certain points mentioned in your documents, such as supporting records for bona fide checks. BUT AT ALL TIMES YOU MUST BE Well Prepared – know your stuff – Know which SOPs/WIs apply, training file up to date Confident, cool, calm, collected Polite at all times – never aggressive Helpful – but only reactively Answer the questions truthfully and only the question asked Act professionally BUT DON’T Guess or say “I think” – you know it or you don’t Lie! – it all ends in tears Get aggressive or be ‘clever’ Fidget, shift around, touch your face etc Volunteer anything not asked for – don’t elaborate on your answers Chat in places the auditor may be ie. toilets, corridors etc ………I am sure you all know this already!

Close Out Meeting

• Clarification of any inspection deficiencies; • Discussion of any remedial proposals.


Presenter

Presentation Notes

So remember…… An Inspector is: a knowledgeable human being has a tough job to do interrogates documentation/systems/people And you : are well prepared, know your job Represent the company in the best possible way Behave professionally Inspectors will find deficiencies as that is what they are there to do, but YOU can implement the right systems and have all the necessary supporting documentation to minimise the severity or number of deficiencies identified.

Post Inspection Letter

• Written confirmation of any inspection deficiencies; – Any deficiencies found will be itemised and

categorised; – Deficiencies are rated as Critical, Major or Other

dependent on the impact to public health

• Letter will advise that response is required within 28 days.



Presenter

Presentation Notes

Normally it is common practice for the inspector to send you a written report after the inspection detailing the deficiencies identified and which legislations/ guidelines they contravene. They would also expect you to provide a CAPA plan with timelines for correcting the deficiencies identified.

Definition of Deficiencies Categories (1)

• Critical Deficiency – Deficiency which has caused or leads to a

significant risk of causing either a product to be harmful to the patient; or

– A combination of a number of major deficiencies that indicates a serious systems failure.


Presenter

Presentation Notes

Any departures from the legislations or guidelines are highlighted as deficiencies and these are usually categorised as critical major and minor or other. Critical being where the deficiency has already resulted in an incident or the business practices contravenes the legislations that would directly impact on patient safety.


• Major Deficiency – A non-critical deficiency which

• has caused or may cause a product not to comply with its marketing authorisation;

• indicates a major deviation from EU Good Distribution Practices;

• indicates a major deviation from the terms and provisions of the wholesale dealers license;

• indicates a failure to carry out satisfactory procedures for distribution of medicines or a failure of the Responsible Person to fulfil his legal duties;

• a combination of several ‘other’ deficiencies, none of which on their own may be major but which together represent a major deficiency and should be explained and reported as such.



Presenter

Presentation Notes

Major deficiencies tend to be a departure from good documentation practices where personnel are failing to follow their procedures or procedures are absent and records not kept up to date.


• Other (minor) deficiency – A deficiency which cannot be classified as either critical

or major, but which indicates a departure from good distribution practice.


Presenter

Presentation Notes

These minor or other deficiencies tend to be suggestions for improvement to existing procedures and records. Please also note that for example a number of minor deficiencies in documentation practices can also be escalated to a major.

Follow-up, Close-out and Sanctions

• Response will be reviewed by the Inspector;

• If the response is acceptable, the inspection will be closed out by letter;

• If unacceptable it will be escalated to an internal advisory group in the event of a critical deficiencies or un actioned deficiencies. © Copyright inglasia pharma solutions Ltd /


Presenter

Presentation Notes

At the end of the inspection and review of the auditee’s responses the inspector will confirm the status of the audit as closed or whether a re-inspection is required and when this follow up inspection will take place. If the audit and responses were satisfactory them a recommendation will be provided on when the next audit will take place.

Most common deficiencies (UK data for 2005/2006)


Description of deficiency Incidence (%) General storage – temperature control & monitoring

16.7

Unauthorised activity 9.6 Lack or inadequate written procedures 8.8 Supplier status 7.9 Cold storage – temperature control & monitoring

7.9

Premises, equipment & calibration 7.0 Cold chain transportation 7.0 Quality system & duties of RP 5.3 Segregation of unsaleable stock 3.5 Returns 3.5

Top 5 deficiencies (UK data for April 2008-March 2009)


Description of deficiency # of times reported

Lack of, or inadequate written procedures 30

General storage - temperature control and monitoring

24

Un-authorised activity 19

Quality system and duties of the Responsible Person

18

Cold storage - temperature control and monitoring 13

General Storage – Temperature Control and Monitoring

• Medicinal products are stored inappropriately. Products stored on mezzanine levels where temperatures in the summer are regularly above 25ºC. At inspection temperature display was 28ºC with a maximum recorded of 37ºC;

• Monitoring & control of temperature records was inadequate: – Temperature ranges have not been properly kept with

frequent gaps in the record; – Temperature records were not available for 2005/2006 at

inspection; – Where temperatures in excess of 25ºC were recorded

there was no record of corrective action; – Temperature monitoring system in warehouse was broken.


What The Inspector Expects to See?

• Temperature map of the warehouse; • Storage area temperatures recorded

daily; • Temperature records reviewed on a

regular basis with any excursions noted and corrective actions taken recorded;

• SOPs in place covering systems for temperature monitoring and excursion handling. © Copyright inglasia pharma solutions Ltd /


Unauthorised Activity

• License holder has failed to inform the licensing authority of changes required to the license in that medicinal products have been stored at unlicensed premises not named on the wholesale dealers license. © Copyright inglasia pharma solutions Ltd /


What The Inspector Would Expect to See

• All procurement, storage, and distribution activities involving medicinal products undertaken by the license holder must be performed in accordance with the WL;

• Competent Authority approval must be

obtained prior to commencing any procurement, storage, & distribution activities involving medicinal products.


Supplier Status

• Control of purchasing of pharmaceuticals is unacceptable:

– UK packs of X and Y product had been

purchased from ABC company in Dubai. Company is outside of the EU and no bona fides of this company have been obtained; Shipment of 507 X tablets have been received from ABC company with no supporting paperwork available.



What The Inspectors Expect to See

• Medicinal products should only be purchased from licensed wholesalers and manufacturers;

• Bona fides of each supplier should be

checked to ensure they are licensed to supply medicinal products. These checks should be documented and the status of each supplier should be assessed at regular intervals. © Copyright inglasia pharma solutions Ltd /


Premises, Equipment and Calibration



• Receiving bays should protect deliveries from bad weather during unloading;

• Reception areas should be separate from storage areas;

• Building should be proofed against the elements; • Storage facilities should be clean and free from

litter, dust, and pests. Adequate precautions should be taken against spillage or breakage, attack by micro-organisms, and cross contamination;

• Temperature monitoring devices should be of the required accuracy and calibrated on an annual basis.


Quality Systems and Duties of The RP

• RP has failed to ensure the conditions of the WL are met and that the guidelines on GDP have been complied with;

• Products have been purchased from

companies where bona fides have not been established contrary to the company SOPs.



• Roles and responsibilities of the RP should be clearly defined; where services of a contract RP are used a Quality Agreement between the company and the RP should be in place;

• Conduct of annual self inspections to demonstrate compliance with the conditions of the WL and GDP;

• Clear documentation of all decisions relating to GDP.


Returns

• Return of products to stock was not subject to sufficient control: – Products that have been outside the

control of the warehouse for a period of time in excess of the company SOP were being returned to stock.



• Segregation of returned medicinal products from saleable stock to prevent redistribution until a decision has been reached;

• For products which have left the care of the wholesaler, these should be returned to saleable stock if: – Goods are in their original unopened containers and in

good condition; – It is known that the goods have been stored and handled

under the proper conditions; – The remaining shelf life period is acceptable

• Records of returns received and formal release by the RP of goods back into stock.



The RP, a summary

Responsible Person – who qualifies?

Sufficient experience

No Academic Pre-requisites.

Detailed knowledge of pharmaceutical directives and guidelines of local region.

Detailed knowledge of the following: 1. Law and Admin 2. Role and Responsibilities

of an RP 3. Storage and Distribution

requirements 4. Aspects of GMP

requirements applicable to GDP

Presenter

Presentation Notes

If an individual is to be named on a Wholesale Dealer Licence, they must have sufficient experience working within the supply chain for medicinal products for Human and Veterinary use. There are no academic qualification pre-requisites to become an RP however suitable core abilities would be GCSE or equivalent level in English and Maths. However in certain EU member states the RP is expected to be a qualified Pharmacist. The individual must have a detailed knowledge of the pharmaceutical Directives and Guidelines applicable to their region. They must also have an understanding of the role of their local regulatory authority in the licensing of medicines and the duties of the authority as an enforcement group. With regards to storage and distribution of medicinal products, detailed knowledge is required in the following areas: The law and it’s administration The Role and responsibilities of the RP The requirements for storage and distribution The principles of GMP Quality Management Systems that apply to GDP


Calcott Consulting consultant to the pharmaceutical & biotechnology industry

Q&A