The document discusses regulatory guidelines for pharmaceutical excipients and their development. It notes that the International Pharmaceutical Excipient Council promotes quality standards for excipients to ensure drug product efficacy, safety and stability. The document outlines challenges in developing new excipients and coprocessing APIs with excipients. It also discusses establishing excipient functionality through specifications and harmonizing pharmacopoeial standards for excipients.

1. Regulatory guidelines for the
pharmaceutical excipients

2. Regulatory guidelines
• In general, excipients are used to improve stability,
manufacturability, and performance of a dosage form.
• The International Pharmaceutical Excipient Council (IPEC)
Federation, a global organization comprising regional
associations organized to promote quality in pharmaceutical
excipients,
• It has been working on guidelines to deal with technical,
safety, and regulatory concerns related to the development
and commercialization of co-processed excipients

3. Example of coprocessing
• Coprocessing of gatifloxacin with stearic acid and/or palmitic
acid was carried out to mask the taste of gatifloxacin for a
pediatric formulation.

4. API-excipient coprocessing approach faces
two big hurdles
• First, the API manufacturing plant also needs to be approved
as a drug product manufacturing plant with relevant GMP
measures in place. The reason for this requirement is that
regulatory agencies consider API-excipient co-processed
material as a drug product intermediate.
• Second hurdle is that once the API-excipient coprocessing
step is complete, the shelf-life clock starts regardless when
the coprocessed API-excipient is converted into a final
product.

5. Development of excipients
There are three routes by which new high functional
excipients can be developed
• To make new grades (pure, extra pure)of the same excipients
or specialized grades of excipients
• To introduce new chemical entities as excipients (necessity
to prove safety profiles and address toxicity issues hence
expensive)
• To produce high functional excipients is by combining two or
more excipients by a simple physical mixture of two or more
excipients

6. Development of excipients
• Excipient manufacturers should use regulatory guidelines to
anticipate technical, safety, and regulatory challenges for the
development of high functionality excipients.
• In the QbD approach, excipient functionality can be
established by using multiple lots and multiple source of an
excipient during product development

7. Development of excipients
• There is no independent pathway to get the approval of a
new excipient prior to its use in a formulation.
• Hence, an approval of an excipient is always tied with the
approval of a drug product.
• Therefore, a formulator has to take a risk by using an
unapproved excipient in the formulation and be prepared to
generate long-term toxicity data to support the excipient use
in the drug product (formulators are reluctant to this)

8. Pharmacopoeial Harmonization
of the Excipients

9. Functionality of Excipients
• Functionality is defined as the property of an excipient
that helps in achieving objectives of quality,
manufacturing ability, and performance of a dosage
form
• It includes chemical and physical properties of the
excipient

10. Functionality depends on
• Chemical and physical properties of excipients
• Amount of by-products or additives present
• Interaction of excipients with other constituents of
formulation
• Stress applied during the processing of product.

11. Functionality-Related Characteristics (FRCs)
• FRCs are controllable chemical or physical
characteristics of excipients that affect their
functionality.
• These specifications focused on ensuring
identification, purity, and quality of excipients

12. FRCs and corresponding FRT

13. Pharmacopoeial Harmonization
• International Pharmaceutical Excipient Council (IPEC) is a global
organization that brings together producers, distributors and
users of pharmaceutical excipients.
• It promotes better quality and optimal use of pharmaceutical
excipients for better pharmaceutical manufacturing of a drug
product
• It supports pharmacopoeia to include a general chapter on
systematic process for evaluation of critical properties of
excipients and test methods related to these properties that
are important for particular formulation

14. Pharmacopoeial Harmonization
• IPEC promotes best use of excipients in dosage forms so that
patient treatment can be improved without affecting the
efficacy, safety, and stability of active ingredients.
• IPEC also ensures that dosage form deliver the promised
benefit to patients
• IPEC has been promoting inclusion of FRCs and FRT
(Functionality-Related Testing) in the mandatory section of
monographs of excipients.

15. European Pharmacopoeia and FRCs
• EP has included FRCs as non-mandatory portion of the excipient
monographs.
• EP while dealing with FRCs mentions that “the following tests are not
mandatory requirements but in view of their known importance for
achieving consistency in manufacture, quality and performance of
medicinal products, it is recommended that suppliers should verify
these characteristics and provide information on the results and
analytical method applied to users. The methods indicated below
have been found suitable however, other methods may be used.”