API Flashcards
What is the purpose of a QP Declaration?
To confirm during a marketing authorisation application that that the active substance has been manufactured in accordance with Good Manufacturing Practice (GMP) for medicinal products for human and veterinary use, Part II: Basic Requirements for Active Substances used as Starting Materials2.
What is the structure of a QP declaration?
It consists of 5 sections a, b, c, d and e
What is in section a of a QP declaration?
a.
Name of AS, name and address of each AS manufacture site from registered starting materials inc intermediate sites. This is especially important for CEPs in case intermediate sites are not named on the CEP.
What is in section b of a QP declaration?
MIA holder details for each site using the material (sites, MIA no, manufacturing activity)
What is in section c of a QP declaration?
Basis of QP declaration
i. Confirm they’ve had a Direct audit
ii. sites audited, auditor details and date of audit. If a contract auditor has been used there’s a table to fill
iii. Supporting info – results of GMP cert by EMA or MRA partner
What is in section d of a QP declaration?
QP declaration of compliance
i. they are QP that can do it
ii. based on audit API made to GMP
iii. auditors are competent and QA agreements in place
iv. Responsibilities in case of approving on behalf of multiple MIAH - the signatory confirming that the declaration is made on behalf of all the involved QPs named on the relevant MIAH(s) and that a procedure defining GMP responsibilities is in place and that technical agreements exist between the named Signatures
What is in section e of a QP declaration?
Name and signature of QP responsible for this declaration - name, status, and MIAH name and number
What are the sources of impurity in an API
Solvents
Catalysts
Side-reactions
Degradation
Nitrosamine creation
Polymorphs
Equipment failure (glass vessels etc for physical, instruments for process)
Processing error (people or machine failure)
Cross contamination from cleaning.
Is it acceptable to reuse solvents in the API manufacturing process?
If testing of the solvents confirms that they are suitable then it is acceptable, How this occurs must be documented and controlled. This is as per Section 14.4 in Part 2 of Vol4.
How would you risk assess excipients?
Route of administration
Impact on quality of dosage form
History of adultery i.e. heparin, propylene glycol, glycerol,
Micro risk: endotoxin, pyrogens
TSE risk
Natural source
What are the potential sources of microbiological contamination of APIs?
Water used in final crystallisation + rinsing step + packaged into API
Starting material: biological or terrestrial origin
Premises: cleanroom design principles
During storage or distribution
What are the main microbial contamination related to plant source APIs?
GPRs – Bacillus
GNRs – especially if fertilised with sewage / manure
Fungi - Cladosporium, Rusarium etc
What are the contents of BP?
6 volumes
Vol 1+2:
Medicinal substances
Vol 3:
Formulated prep: General monographs
Formulated prep: Specific monographs
Vol 4:
Herbal drugs, prep and medicinal products
Materials used in homeopathic preparations
Blood related products
Immunological products
Radiopharmaceutical prep
Surgical materials
Vol 5:
Appendices
IR ref spectra
Index
Vol 6:
BP vet
What are the objectives in API process development?
Determine structure of API (proof of structure)
Develop synthetic route suitable for commercial scale MFG + validation
Develop IPC
ID and quality impurities
ID polymorphs
Develop test methods and specifications
Investigate chem stability
ID degradation products + detection method of all impurities
Transfer process into production
What are the strategies to control cross contamination in API MFG?
Separation of critical activities and certain product categories
Layout designed to give suitable: material flow + personnel access + maintenance access
Finishes to allow adequate cleaning and attainment of req EM standard
Ventilation system to provide product protection
