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Report

March 31

British Pharmacopoeia set to change Monographs for finished products requiring dissolution testing.

Dissolution testing is a well-established method for determining if a product will release its active pharmaceutical ingredient within specified time limits. Many manufacturers utilise the methodologies described in the various pharmacopoeias, with the British Pharmacopoeia being prevalent for products being released onto the UK market.

The British Pharmacopoeia has two types of criteria that are to be applied to conventional release solid dose forms dependant on when the monograph for a particular product was published. For product monographs published after 2008, the harmonised acceptance criteria, “Q”, as described under Appendix XII B are applied, where “Q” is the specified amount of dissolved active substance released into solution within a specified time. Typically, “Q” values and Times are specified in the monograph, or where applicable, in Product Specifications an example being 75% released in 45 minutes.

However, for monographs published prior to 2008, supplementary chapter SC I E. Dissolution Testing of Solid Oral Dosage Forms directs the analyst to section Monographs of the British Pharmacopoeia under Appendix XII B which states that these products must have 70% of their active substance in solution within 45 minutes.

A large number of BP finished product monographs for solid oral conventional release dosage forms do not refer to the “Q” acceptance criteria within the monograph, and for prolonged-released forms, a Production Statement is included rather than a dissolution test. This can lead to confusion as to which limits to apply to any given product and highlights that an inconsistent approach must be applied across a manufacturers product portfolio.

For this reason, the British Pharmacopoeia Expert Advisory Groups on Pharmacy are considering several approaches that may be applied to all product monographs. One solution proposed is to apply the harmonised acceptance criteria retrospectively to all product monographs published prior to 2008. Whilst this would increase consistency in terms of how product dissolution rates are assessed, it would potentially leave Market Authorisation Holders (MAH) with non-compliant products that cannot meet newly applied criteria. If this were discovered after any updates to specific monographs, it could take the BP Commission up to 18 months to further update the monograph.

To aide in the decision-making process, the BP Commission is asking industry for input on this matter. MAH in particular are being asked to highlight any concerns that may arise from any changes to the acceptance criteria for dissolution. The following questions are being asked by the BP Commission;

  • What are your general comments on the current situation in the BP and how could it be improved?
  • For monographs requiring dissolution testing, what methods would be useful to include to enable users to carry out the test?
  • Should multiple dissolution methods be included in the BP to reflect the methods used for available products?
  • Do you believe that dissolution tests and acceptance criteria should be included in BP monographs for pro-longed release preparations? What test would be proposed?
  • Should “Q” acceptance criteria be included in the BP for solid oral dose forms in future new monographs or included as part of a revision for current monographs?
  • How could “Q” values be set to ensure that they are appropriate for the preparation?
  • What criteria are important to consider in a compendial quality standard when setting the acceptance criteria for dissolution testing.

This is a really great opportunity for the Pharmaceutical industry to influence how its products will be assessed, as well as ensuring that currently marketed products continue to meet strict quality standards. The deadline for comments to the BP is 07 April 2017, so to ensure that any concerns are highlighted to the BP Commission, email bpcom@mhra.gsi.gov.uk (with “Dissolution Consultation” as the subject line) as early as possible. Again, it can take the BP up to 18 months to update specific monographs, so if industry doesn’t take this opportunity to have its say it could mean a great number of products are no longer compliant.

A list of product monographs published prior to 2008 is included in the current edition of the British Pharmacopoeia under supplementary chapter SC I E. Dissolution Testing of Solid Oral Dosage Forms and includes many common product forms including; Paracetamol Tablets, Ibuprofen Tablets, Folic Acid Tablet and Prednisolone Tablets to name a few. It is recommended that MAH review the requirements for dissolution testing for their own products and familiarise themselves with the different approaches taken by the BP for those products and contact the Commission to voice their thoughts.

Broughton Laboratories have been invited to be on the development panel for the update of the dissolution aspect of the BP.  We understand that his will have a real impact on MA holders. Changes are coming to the British Pharmacopoeia monographs for finished products requiring dissolution testing. You only have until the 7th of April 2017 to submit your comments. We would advise you to contact the BP directly so that you can email bpcom@mhra.gsi.gov.uk (with “Dissolution Consultation” as the subject line).

About the Author

Emmet Tilley is a Quality and Compliance Supervisor at Broughton Laboratories. Emmet graduated from the University of Huddersfield with a BSc in Forensic and Analytical Science and started his career at Broughton Laboratories as an Analytical Chemist in 2007. After finding his passion in data review and verification activities, he transferred his skills to the quality department in 2011 where he remains committed to maintaining the company’s compliance history as well as ensuring patient safety.