Within the last months FDA and EMEA have put their regulatory focus on
comparability and similarity of biotechnological/biological medicinal
products.
Last week alone three new guidances – two draft,
one final – were published by FDA and EMEA.
It is very important to clarify that these documents
cover two completely different topics. Although the technical terms used
within these documents might be identical.
One topic is the comparability of biotechnological
products that are subject to process changes – before and after the
change. The other one is the comparability of a reference biological
medicinal product with a similar biological medicinal product.
Concerning the first issue, FDA has published the
final Guidance for Industry "Q5E Comparability of
Biotechnological/Biological Products Subject to Changes in Their
Manufacturing Process". This ICH document came into operation in the
European Union (EMEA) in June as well.
The aim of the proposed comparability studies is to
show that pre- and post-change products have similar attributes concerning
quality, safety and efficacy.
Some important statements of this comprehensive
document should be pointed out:
- Most of the subchapters end with the phrase
"… it might be necessary to conduct nonclinical or clinical
studies …". This is the worst-case scenario for process changes
- a fact one has to keep in mind at the very beginning of considering
a process change. Therefore, the first question you have to ask
yourself is: What is the impact of the process change on quality
findings, the nature and the level of knowledge about the product and
the existing nonclinical and clinical data.
- The guidance distinguishes clearly between
marketed products and products in development. Process changes are
expected in a much wider range during development. For early phases of
nonclinical and clinical studies less extensive comparability studies
are required.
- Words that are used frequently in this guidance
document are: justified, consideration, evaluation. Due to continuous
brainwashing all people working in a GMP environment are aware of the
importance of traceable documentation. But for the scientifically
sound assessment of the change in the manufacturing process you will
be glad if you get comprehensive documentation from your colleagues in
R&D. So you better tell them in advance!
You can download the pdf version of the document
here:
http://www.fda.gov/cber/gdlns/ichcompbio.pdf
The draft guidelines that were released by EMEA last
week deal with the issue of biosimilarity. Both documents "Guidance
On Biosimilar Medicinal Products Containing Recombinant Granulocyte-Colony
Simulating Factor" and a "Guidance On Biosimilar Medicinal
Products Containing Recombinant Erythropoietins" are Annexes to the
"Guideline On Similar Biological Medicinal Products Containing
Biotechnology-Derived Proteins as Active Substance: Non-Clinical And
Clinical Issues". The deadline for comments is October 2005.
Due to the impressive number of papers that have
been released by EMEA on biosimilarity it is important to understand their
structure.
The core "Guideline on Similar Biological
Medicinal Products" (CHMP/437/04) was released for consultation in
November 2004. The phase for comments ended in February 2005. A final
version has not been published yet.
Based on this document two further guidelines were
brought out dealing with quality issues (EMEA/CHMP/BWP/49348/2005) and
non-clinical and clinical issues (EMEA/CHMP/42832/2005). For the first one
the deadline for comments was June 2005; for the second one it will be
October 2005.
In addition EMEA has edited four annexes to the
guideline on non-clinical and clinical issues focussing on certain
biological medicinal products: Somatropin (EMEA/CHMP/94528/2005),
Recombinant Human Insulin (EMEA/CHMP/32775/2005), Recombinant
Erythropoietins (EMEA7CHMP/94526/2005) and the Recombinant
Granulocyte-Colony Stimulating Factor (EMEA/CHMP/31329/2005).
All draft documents can be downloaded from the EMEA
homepage at
http://www.emea.eu.int/htms/human/biosimilar/biosimilarcon.htm.
It is crucial to know that there are extra
guidelines on APIs. These documents cover both aspects of comparability
exercises: due to process changes and for "similar" products.
The Doc Refs are EMEA/CPMP/3097/02/Final and EMEA/CPMP/BWP/3207/00/Rev 1.
Life could be so simple!
|
