Roles and Duties Flashcards
What are potential KPIs of a QMS
Recalls
Complaints
Product returns due to errors
OOS
Rejected lots
Deviations and investigations
Internal and external audits
Adherence to programme and findings
CAPA closeout
Reworked batches
PQRs done on time
What would you expect to see in a Batch record
Product name/strength and dosage form
Dates and time: Start + significant steps + completion
Names: who did what + approved sig list + initials
Check of critical operations: Weighing + dispensing + reconciliations
Specific batch number / analytical reference
Results of IPC
Reconciliation data for production yields
Critical info: sterilisation records + EM reports + QC test results
Deviations/atypical events
Legal basis for QP
Required to have one in 2012/1916 schedule 7 and
2004/1031 part 6 para 43
2013/2033 schedule 2 para 11
Along with EU 536/2014
2017/1569 and 1572
2001/83/ec article 51
What are the ICH Q1 a-f?
ICH Q1A Stability Testing of New Drug Substances and Products
ICH Q1B Photostability for new DS and DP
ICH Q1C New dosage forms
ICH Q1D Bracketing and Matrixing
ICH Q1E Evaluation of stability data
ICH Q1F Registration in Climatic Zones III and IV
Requirements for QPs as contractors?
- Indemnity insurance
- Follow code of conduct and what you would do as a new QP.
What would you do if you were a new contractor somewhere?
- Getting onto the license – variation submitted, updated copy received. Review this, get to know the sites and supply chains (SCM)
- Training in the background, formulation and theory behind the product your manufacturing
- Read the PIL / SmPC
- Get familiar with the PQS. QPs have a responsibility for overall quality / ensuring GMP is maintained as well as releasing to the MA. This includes how it’s performing as well as how it should be implemented. Gap analysis of PQS against routine duties / annex 16.
- Have a read of the latest health authority and internal site audits, see if there are any areas for working. Anything like a QIP?
- So give the MA a read, see how we should be manufacturing it
- Read the PQR to see how it’s performing. Any product performance meetings etc see how manufacture is and if there are any common issues / trends to watch out for
- PQS – SOPs in place for critical processes throughout site, PQRs performed – how many on time?
- Premises and Equipment – facilities routinely maintained, PPM, EM of clean areas and water systems. How do water systems work?
- Personnel – training systems in place, how do we train out SOPs, how many overdue events, review last annual GMP training pack
- Documentation – records and instructions, so review technical reports, BDs etc. How is the MA translated into useable information for staff and QP?
- Production – how is this managed, spend some time there, getting to know the people processes, site tours etc. Review self-inspections of critical processes. Review control strategies, see how these are translated from the MA into useable information
- Quality control – what testing do we do, how is this performed, procedures / method control and performance of the lab (lab investigations, deviations, compliance, self-inspections)
- Validation - review the process for equipment, lab methods and production
- Outsourced activities – do we have any, what are they, can I see the audits. Are we sure that they’re not further outsourced without us knowing about it?
- Make sure there are systems for complaints, recalls, returns, deviations and change management and ensure I have access to all of them. Look at examples, understand how those systems work.
- Review self-inspection process, ensure we have one
- Shadow existing QPs, learn from them. Shadow anyone who’ll have you tbh.
- API declarations
- Sampling – reference and retention samples
- Process should take at least a couple of months to get familiar with the PQS, see how the routine duties are performed and to understand the process.
What is the process of batch release as outlined in Annex 16?
- Batch release is a 3 stage process:
o Checking manufacture and testing in accordance with release procedures
o QP certifies that the batch conforms with the MA
o Stock is moved to released / saleable status
What are the requirements for UXD from Annex 16?
Annex 16. States that if you have a deviation whereby you go outside the MA process but everything tests in spec then if you can certify the batch if you know the root cause and CAPA it
Considerations would be that you have considered impact on safety, stability, and in the case of biologics be afraid because of the complex nature of the molecule and it’s structure. Also that the QP certifying should be aware of the unexpected deviation, so I would be ensuring this is called out in TAs
What are the requirements for travel samples from Annex 16?
1) Audit
2) Scientific Study - description of how and conditions, results equivalence, assess impact of time difference
3) periodic / random comparative results
4) unexpected result or OOS - potential implications for sampling at other site, inform CA of sampling site. Investigate as a complaint
What is risk management?
- Risk management is the identification, evaluation and subsequent prioritization and management of risks.
- Based on ICH Q9, in that severity x harm = risk. You can use tools to identify and manage risks, for example FMEAs.
- Applied throughout the GMP guidance. Pretty much all the chapters talk about it - chapter 1 in that when applying a PQS it must be of a size and ability commensurate with the activities taking place and the risks within it. Personnel - training based on risk, for example the more complex process carry more risk therefore need more training. Prem / eqpt, EM in hot spot locations. Documentation - OpTRAs, cleaning risk assessments, forms an inherent part of the PQS
What are the two main principles of ICH Q9 QRM?
The evaluation of risk to quality should be based on sci knowledge and ultimately link to the protection of the pt
The level of effort, formality and documentation of QRM process should be commensurate with the level of risk
What are the steps of QRM?
Rx ID
Rx analysis
Rx evaluation
What are the legal duties of a QP?
a. That each batch manufactured within the United Kingdom has been manufactured and checked in accordance with national legislation and the MA (or herbal registration or equivalent authorisation)
b. If a product is imported from a country that’s not on the Approved Countries for Import list, then each batch has undergone within the UK or an approved country, a full qualitative analysis, a quantitative analysis of at least each API and all the other tests or checks necessary to ensure quality in accordance with the MA. , irrespective of whether the product originated from the UK or an approved country
c. if required, Safety features are in place
d. Certified in a Register for at least 5 years.
What are the routine duties?
PAPERWORK
Technical Agreement in Place (18)
Audit of sites of manufacture and testing up to date and reports available (3)
Supply chain maps available (2)
TSE certificates compliant with MA (10)
Source and spec of starting materials and packaging compliant with the MA (6). QMS ensures only good materials have been supplied (i.e. IMQC).
INCOMING CHECKS
Active made to GMP and distributed to GDP (7)
Excipient made to sufficient GMP, as defined by a risk assessment (relevant GMP as per 46(f)) (9)
Imported Api for human drug product has been made to GMP equivalent to UK and if not on UK Approved Countries list then accompanied by written confirmation from competent authority that they are subject to unannounced inspection and any failings will be immediately notified (8)
MAKING
Made and tested to GMP (1)
Records complete and endorsed by appropriate personnel. All IPCs done (11)
Validation: Manufacturing and testing remains in a validated state and personnel are trained and qualified. (12)
Safety features have been applied. (21)
TESTING
Made and tested to the MA (5)
Finished test data complies to spec in MA or RTRT programme (13)
Post marketing commitments addressed and stability data supports certification (14)
Self inspection programme is active and current (19)
CERTIFYING
Planned changes at a suitable place to allow certification - any required additional testing is complete. (15)
All sites of manufacture, analysis and certification compliant with MA for intended territory (4)
Deviations / LIRs / investigations complete sufficient for certification (16)
Appropriate arrangements for distribution and shipment are in place (20)
Complaints investigation and recalls don’t negate certification (17)
Which routine duties are not required for IMPS?
Safety Features
Post Marketing Commitments
Excipient and Imported API GMP
Validation (other than methods, cleaning and sterilisation)
