Pharmaceutical Deformulation and Beyond
What is pharmaceutical deformulation?
Excipient quantification and Identification
The process of analytically breaking down a material or product’s formulation into separate components and determine the specific identity and exact quantity of constituent components is called deformulation of pharmaceutical formulations. The knowledge of excipient characteristics and our dedicated analytical laboratory facilities, methodologies and procedures, enables us to offer excipient quantification and identification of individual excipients in a pharmaceutical formulation.
Customers approach us for our deformulation services for several reasons:
- For specific biowaiver bioequivalence (BE) strategies Q1/Q2(Q3) deformulation may be required to produce a generic product that exactly matches a drug on the reference list or the comparator medicinal product
- To investigate a competitive or reference formulation
- To determine if patents have been infringed
- To improve an underperforming formulation
Pharmaceutical deformulation services: determination of excipient grade and source
Our experience in excipient characterization and deformulation of pharmaceutical formulations gives us the opportunity not only to identify and quantify individual excipients in a complex pharmaceutical formulation, but often also confirm the excipient grade, excipient quality and sometimes even the excipient source of the ingredients.
Our deformulation services go further than quantifying excipients; read more about our complementary reverse engineering services.
Bioequivalence, essential similarity, and Q1/Q2 formulation Assessments
Excipia’s pharmaceutical deformulation services have been successfully applied in biowaiver bioequivalence (BE) strategies for complex generics, to provide Q1/Q2 formulation assessment data or proof essential similarity to a reference product. For certain types of products, FDA’s regulations generally require that proposed Q1/Q2 products be qualitatively (Q1) and quantitatively (Q2) the same as the reference listed drug (RLD) with respect to inactive ingredients.
Similarly, the EMA defines in extended pharmaceutical equivalence acceptance criteria that the nominal quantitative composition of excipients should be the same or differences not greater than ±5% or 10% with respect to comparator medicinal product .
These specific BE approaches may be recommended in product-specific guidance for generic Q1/Q2 formulations, like
- Parenteral suspension, emulsion, and liposome,
- Ophthalmic ointment, suspension and emulsion
- Otic suspension
- Orally inhaled and nasal drug products (OINDPs)
- Topical dermatological products
- Oral drug products
Such Q1/Q2 product biowaiver approach can be considered acceptable, provided there is no significant difference between the products in terms of the qualitative and quantitative composition of excipients; Test (T) and Reference (R) contains the same active and inactive ingredients in the same concentration (Q1/Q2) as the RLD product. In this context, “sameness” refers to situations where the qualitative (Q1) and quantitative (Q2) properties, as well as the arrangement of matter (Q3) in the test and reference products, are considered to be the same.
Q1: Qualitative sameness; identity of an inactive ingredient.
- Means that the test product uses the same inactive ingredient(s) as the reference product. An applicant should provide detailed information on the chemistry and grade of each inactive ingredient, and characterization data, if needed for inactive ingredients.
Q2: Quantitative sameness; quantity of an inactive ingredient
- Means that concentrations of the inactive ingredient(s) used in the test product are within ±5% of those used in the reference product. An applicant should determine the difference (%) of an inactive ingredient in the Test (T) and Reference (R) products, i.e., [ (T-R)/R ] x 100).
Excipia’s pharmaceutical deformulation services and techniques can quickly provide solid and precise Q1/Q2 data. Our experiences employees have years of experience and know-how to extract, identify and quantify all components of pharmaceutical formulations.
Combined Deformulation, Pharmaceutical and Dissolution lab Services
Often the development of pharmaceutical formulations of a generic product can be accelerated and improved if a reference product is well characterized. And then not only in terms of the release properties, but also when the product is deformulated and the exact formulation composition, both excipient quality and excipient amount, is revealed. Decoding the quantitative details will drastically reduce the number of experiments required to reach the optimal formulation.
Thanks to the unique combination with a pharmaceutical development and dissolution testing services within Avivia, we can provide comprehensive insight into different product properties, such as detailed release performance, product composition or insight into the applied production techniques or processes.
If desired, we can reconstruct a copy of the product.
Case study deformulation services: bioequivalent product development
Fixed dose combination product (example)
Avivia colleagues were approached by a client to develop a discriminatory dissolution method for a complex fixed dose combination product after failed bioequivalence studies.
A CDA was put in place and information was exchanged. After evaluation of the product formulation and (bio)analytical data by an internal multidisciplinary expert team, the team made a proposal to the customer to first deformulate the reference product and possibly adapt the formulation of the test product accordingly.
After complete deformulation of the pharmaceutical reference product, qualitative sameness was confirmed, however important differences in quantitative composition were revealed.
The formulation was modified, confirmed improved delivery of the active pharmaceutical ingredients through dissolution testing, and then successfully passed the following bioequivalence study.
Read more about our reverse engineering services.
Fixed dose combination product (example)
Avivia colleagues were approached by a client to develop a discriminatory dissolution method for a complex fixed dose combination product after failed bioequivalence studies.
A CDA was put in place and information was exchanged. After evaluation of the product formulation and (bio)analytical data by an internal multidisciplinary expert team, the team made a proposal to the customer to first deformulate the reference product and possibly adapt the formulation of the test product accordingly.
After complete deformulation of the pharmaceutical reference product, qualitative sameness was confirmed, however important differences in quantitative composition were revealed.
The formulation was modified, confirmed improved delivery of the active pharmaceutical ingredients through dissolution testing, and then successfully passed the following bioequivalence study.
Read more about our reverse engineering services.
