Risk Classification of Excipients Presentation to Stakeholders Meeting Brussels 14 th May 2009 Frithjof Holtz
Risk Classification of Excipients 1. Why Classification? 2. How will Classification work? 3. Communication of GMP Level
Why classify? The aim of classification is to enable manufacturers to choose an appropriate level of GMP for excipients to optimize the assurance that they are suitable for their intended use
Risk Classification of Excipients 1. Why Classification? 2. How will Classification work? 3. Communication of GMP Level
Excipient Classification Assessment Decision Tree Risk Factors The following factors are identified as being the most significant in conducting the excipient classification: Route of administration of final dosage form (contaminants and microbes could bypass body s natural defences; higher level of GMP can help to control and minimize risks ) Function of the excipient (impact on the bio-availability of an active ingredient; higher level of GMP will limit the degree of excipient variability)
Excipient Classification Guidance on the Key Risk Factor Route of administration The main routes of administration of the final dosage form in increasing order of risk and their corresponding risk factors, are: Unbroken skin Oral Compromised skin Mucus membranes Inhalation, intranasal Eye/ocular Parenteral Foundation Level Foundation Level Foundation Level Foundation Level Foundation Level Intermediate Level Intermediate Level
Excipient Classification Guidance on the Key Risk Factor Function of the excipient The main functions of an excipient in increasing order of risk and their corresponding risk factors, are: Excipient does not remain in the dosage form Little or no impact on Active bio-availability Moderate impact on Active bio-availability High impact on Active bio-availability Foundation Level Foundation Level Intermediate Level High Level
Excipient Classification Are there other Risk Factors? The excipient manufacturing process The dose of the excipient and or the proportion of the excipient in the drug product These risk factors have not been included in the risk assessment because they are already sufficiently covered by the Foundation level GMP (IPEC-PQG GMP Guide) concerning e.g. contamination from the raw materials or the process the drug product Marketing Authorisation review and approval process Are there any others?
Excipient Classification Assessment Decision Tree If there are no legal or customer (final drug manufacturer) requirements the classification risk assessment is conducted. The route of administration or function carrying highest risk is used to determine the GMP level. Example: The route of administration is parenteral (intermediate level), but the function is critical impact on Active bio-availability (high level) The applicable GMP Level is high The route of administration is oral (foundation level), but the function is moderate impact on active bio-availability (intermediate level) The applicable GMP Level is intermediate
Excipient Classification
Excipient Classification Manufacturers and Users Assessment of GMP Level Determination of Risks Phase 3 Each party should determine the risks and determine the GMP required for the excipient. Where the results of these assessments differ, the parties should exchange sufficient information to allow a resolution of the differences. If the two parties come to an agreement then that level of GMP is expected to be used in the manufacture of the excipient. An agreement may not be possible in all cases, but if supply is essential then the Qualified Person may still be able to permit the qualification of the excipient manufacturer.
Risk Classification of Excipients 1. Why Classification? 2. How will Classification work? 3. Communication of GMP Level
Communication of GMP Level The level of GMP used in the manufacture of the excipient should be communicated through the supply chain to the user by at least one of the following; an Excipient Information Package marketing literature, the product label the Certificate of Analysis. This communication is of particular importance for excipients supplied via a distributor where no direct communication link may exist between the excipient manufacturer and end user.
Excipient GMP GDP Certification None of this is realisable without the commitment and contribution of all the volunteers to the various working parties and the Steering Committee I thank them for all their efforts Thank you for your attention