Role and requirements of excipients in pharmaceuticals. Summary of new EU guideline published in March 2015 concerning risk assessment of excipients and excipient manufacturers.

1. Excipients and GMP
May 2015
M.Sc. (Pharm.) Eija Hartikainen
Ph.D. (Pharm.) Liisa Mälkki-Laine

2. 18.3.2022 2
GMP for Excipients – Why Not Sooner?

3. What are Excipients?
• All substances used in the manufacturing process and
composition of a medicinal products except drug
substances and packaging materials
• Excipient content of medicinal products, on average 80%
• Needed for several purposes, e.g.
• To facilitate the manufacturing process
• For stability
• To control disintegration, release and absorption
• For identification of medicinal products
• To increase medication compliance
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4. • Composition and Batch Formula (3.2.P.1 and 3.2.P.3.2)
• Choice and Compatibility (3.2.P.2)
• Manufacturing Process (3.2.P.3)
• Excipients (3.2.P.4)
• 3.2.A.2, 3.2.A.3 and 3.2.R, if required
• Specifications of Finished Product (3.2.P.5)
• Stability of Finished Product (3.2.P.8)
 Proof of GMP not required in dossier
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Excipients in Module 3

5. • Monograph in the European Pharmacopoeia:
specifications according to the monograph
• Reference to other pharmacopoeias possible if EP
monographs do not exist
• If not in any Pharmacopoeia, specifications according to
EU guidelines
• EMEA/CHMP/QWP/396951/2006 and ICH Topic Q6A
 Quality of manufacturing and cooperation with
finished product manufacturer will play a bigger
role in the future
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Quality of Excipients

6. EU Guidance
• In 2011, Directive 2001/83/EC was amended to prevent falsified
medicines
• Finished product manufacturer is required to ascertain appropriate
GMP for excipients
• Formalised risk assessment should be done
• Guideline published in March 2015
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7. Guideline in a Nutshell
• Evaluate the risk profile for excipient
• Determine appropriate GMP based on type and use of
excipient
• Gap analysis of the required GMP against the GMP actually
used by the excipient manufacturer
• Evaluate excipient manufacturer’s risk profile
• Establish control strategy for different risk profiles
• On-going risk review and change of strategies, if required
 Deadline March 21, 2016
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8. Challenges
• Determination of appropriate GMP
− Finished product manufacturers have different requirements and
strategies
− Different requirements for the same excipient depending on the use
+ EXCiPACT and other standards facilitate the process
• Difficulties in getting documentation and time slots for audits
− Especially challenging for small manufacturers
− Availability of special excipients may be endangered
+ EXCiPACT and other standards facilitate the process
• Costs
− Vast workload -> Prices will increase?
− Consolidation of excipient markets?
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Appropriate
GMP
Gap
analysis
Risk profile
of excipient
manufacturer
Ongoing
risk
review
Risk
profile of
excipient

Patient safety
Summary