Duties of key personnel in GMP – Part 1 (Production, QC and the QP)

Three key personnel are named on a pharmaceutical manufacturing site’s Manufacturing Licence. These are the Head of Production, the Head of Quality Control and the Qualified Person(s). Their roles and responsibilities are also defined in GMP in Chapters 2 (Personnel) and Annex 16 (Certification by a Qualified Person and Batch Release). These individuals have a major influence on product quality and GMP. Their duties are described below:

Head of Production (EU GMP, Clause 2.5)

Products produced and stored according to appropriate documentation.
Approval of production instructions and their strict implementation.
Ensure production records are evaluated prior to sending to QC.
Maintenance of department, premises and equipment.
Validations performed.
Initial and on-going training.

Head of Quality Control (EU GMP, Clause 2.6)

Approve or reject materials.
Evaluate batch records.
Ensure all testing performed.
Approve specifications, etc.
Approve and monitor contract analysis.
Maintain department, premises and equipment.
Validations performed.
Initial and on-going training.

Duties of the Quality Control Unit (21CFR211.22)

One of these individuals can be found in USA GMP.

Approving or rejecting all components, drug product containers, closures, in-process materials, packaging material, labelling and drug products.
Review production records.
Ensure that if errors have occurred, that they have been fully investigated.
Approving or rejecting drug products manufactured, processed, packed or held under contract by another company.
Approving or rejecting procedures or specifications.

Shared duties of the Heads of Production and QC (EU GMP, Clause 2.7)

Authorisation of written procedures and other documents.
Monitoring and control of the manufacturing environment.
Plant hygiene.
Process validation.
Training.
Approval and monitoring of suppliers.
Approval and monitoring of contract manufacture.
Designation and monitoring of storage conditions.
Retention of records.
Monitoring of compliance to GMP.
Inspection, investigation and taking samples.

The Qualified Person (EU GMP, Clause 2.4 and 1.5 (final paragraph))

Products manufactured within EU – a QP must ensure that each batch was produced and tested according to GMP and Licensed conditions
Products manufactured outside the EU – a QP must ensure that each imported batch has undergone, in the importing country re-testing and evaluation
A QP must sign a register to state that the above has been performed satisfactorily before product is released (QP certification)
Product Quality Review performed in a timely manner and accurate (EU GMP 1.5)

The Qualified Person (EU GMP, Annex 16 Section 8)

Before certifying a batch prior to release the QP should ensure that at least the following requirements have been met:

The batch and its manufacture comply with the provisions of the marketing authorisation
Manufactured according to GMP, or if imported from a third country, according to standards at least equivalent to EU GMP
Manufacturing and testing processes have been validated
Account has been taken of the actual production conditions and manufacturing records (NB The Heads of Production and QC are ultimately responsible for performing this task)
Deviations or planned changes in production or QC have been authorised by the persons responsible in accordance with a defined system
Changes requiring variation to the marketing or manufacturing authorisation have been notified to and authorised by the relevant authority
All necessary checks and tests have been performed, including any additional sampling, inspection, tests or checks initiated because of deviations or planned changes
All necessary production and QC documentation has been completed and endorsed by the staff authorised to do so
All audits have been carried out as required by the quality assurance system

The QP should in addition take into account any other factors of which they are aware of which are relevant to the quality of the batch

Of note is that there is no mention of a Quality Assurance Manager or an Engineering Manager. Most firms have these two individuals, who both have a massive impact on GMP and Product Quality. In Parts 2 and 3 of this post we will look at what their routine duties often are.

Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.

Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.

While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.

About the author

Andy Martin

Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.

Training courses on Annex 1

There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.

More details