A
generic drug is identical, or bioequivalent to a brand name drug in dosage
form, safety, strength, route of administration, quality, performance
characteristics, and intended use.
Generic medicine should be pharmaceutically equivalent to the Reference listed drug which is simply called as RLD. It the prime responsibility of the Formulation scientist to produce the desired dosage form. Formulation and development is not a single step process it takes lots of efforts. Each company only after market analysis ask the F and D department to proceed for Formulation and development.
Generic medicine should be pharmaceutically equivalent to the Reference listed drug which is simply called as RLD. It the prime responsibility of the Formulation scientist to produce the desired dosage form. Formulation and development is not a single step process it takes lots of efforts. Each company only after market analysis ask the F and D department to proceed for Formulation and development.
Requirement
of Generic medicine
- Contain the same API as the
innovator drug (inactive ingredient may vary)
- Be identical in strength,
dosage form, and route of administration to RLD
- Have the same use
indications as RLD
- be bioequivalent to RLD
- meet the same batch
requirements for identity, strength, purity and quality
- be manufactured under the
same strict standards of GMP regulations required for innovator
products
As a
formulation scientist I have summarized some of the steps which will be helpful
to the generic player to develop a new product.
Literature study
I have listed some of the points which have to be
taken care of during formulation development. The details of the medicine can
be accessed form websites. I recommend you to
follow always standard and genuine websites. I have listed some
of the websites with links.
1. eMC(electronic medicines compendium )- emc
2. DailyMed - DailyMed
3. Medscape- Medscape
4.USFDA- USFDA
Above links provide sufficient information well as guideline. The
detail literature can give following details :
· 1. Name of the medicinal product
· 2. Qualitative and quantitative composition
· 3. Pharmaceutical form
· 4. Clinical particulars
· 4.1 Therapeutic indications
· 4.2 Posology and method of administration
· 4.3 Contraindications
· 4.4 Special warnings and precautions for use
· 4.5 Interaction with other medicinal products and
other forms of interaction
· 4.6 Fertility, pregnancy and lactation
· 4.7 Effects on ability to drive and use machines
· 4.8 Undesirable effects
· 4.9 Overdose
· 5. Pharmacological properties
· 5.1 Pharmacodynamic properties
· 5.2 Pharmacokinetic properties
· 5.3 Preclinical safety data
· 6. Pharmaceutical particulars
· 6.1 List of excipients
· 6.2 Incompatibilities
· 6.3 Shelf life
· 6.4 Special precautions for storage
· 6.5 Nature and contents of container
· 6.6 Special precautions for disposal and other
handling
· The
literature study also includes the detailed physiochemical property of the
API. This can be obtained from the supplier. One need to consider all the
formulation variables, either process variables or the component variables.
Following image shows the clear idea about the drug product.
· Nowadays
, Design of experiment is used but in context of Nepal, a simple hit and trial
method is used. Before design of experiment on has to establish Quality target
Product Profile.
· Quality
Target Product Profile for the ANDA Product
The
quality target product profile forms the basis of design for the development of
the product. Considerations for the quality target product profile could
include:
• Intended
use in clinical setting, route of administration, dosage form, delivery systems
• Dosage
strength(s)
• Container
closure system
• Therapeutic
moiety release or delivery and attributes affecting pharmacokinetic
characteristics (e.g., dissolution, aerodynamic performance) appropriate to the
drug product dosage form being developed
Drug
product quality criteria (e.g., sterility, purity, stability, and drug release)
appropriate for the intended marketed product
· But
lattice design can be the easiest way for the various trails planning. The each
critical parameters has to considered. The literature study gives the
excipients but not the grades so as per the target product profile and the
process selected the excipients grade selection is equally important.
The
excipient grade and the amount of excipient is important to control the quality
of the dosage form. A formulation scientist should be well aware about the
excipient grades and its rationale use. An excipients should able to impose its
property over all the drawbacks of physical property of the API. A good
excipients :
a.
Controls the process variables
b.
Enhance stability
c.
Improves Drug release parameters
d.
Control Drug release
e. Mask
the taste and enhance the palatability.
f.
Improve bioavaliablity
g. Reduce
the processing cost and improve the product quality.
Excipients
Selection
The
excipients chosen, their concentration, and the characteristics that can
influence the drug product performance (e.g., stability, bioavailability) or
manufacturability should be discussed relative to the respective function of
each excipient. This should include all substances used in the manufacture of
the drug product, whether they appear in the finished product or not (e.g.,
processing aids). Compatibility of excipients with other excipients, where
relevant (for example, combination of preservatives in a dual preservative
system), should be established. The ability of excipients (e.g., antioxidants,
penetration enhancers, disintegrants, release controlling agents) to provide
their intended functionality, and to perform throughout the intended drug product
shelf life, should also be demonstrated. The information on excipient
performance can be used, as appropriate, to justify the choice and quality
attributes of the excipient, and to support the justification of the drug
product specification.
As the API
is always fix in the dosage form so a formulation scientist is able to play
with the excipients and the process.
Logical
selection of the excipients is always superior in terms of Quality. A well
characterised excipients always give predictable and reproducible
results.
Compactibility
Compactibility study is necessary.
So API compatibility study is done at various proportion and it is checked at
various condition.
Formulation
During
formulation and process development, the formulation scientist should follow
those steps which can be reproducible. Precaution should be taken in those
steps which may create problem in scale-up. Each step should be note down
clearly. Before planing each batch all the process variable which has impact on
the characteristic of the dosage form, has to be considered so that it will
help during optimization of the batch. During the process each inprocess
Quality control test need to be controlled. Care has to be given for
Relative Humidity if the API is moisture sensitive.
Books for
the formulation of each dosage for will be provided in request.
Invitro
evaluation
In vitro
evaluation is done as per the pharmacopoeial requirement. The RLD in most
of the cases disclose the analytical process. A narrow range is
established by the scientist himself so that during scale up the product won't
deviate away from the limit.
Stability
Stability studies are an essential
component of pharmaceutical development, allowing evaluation
of active pharmaceutical ingredient (API) stability or
drug product stability under the influence of a variety of
environmental factors such as temperature, humidity and light. It will be
written more in detail in upcoming post.
-Kabin Maleku
Researcher
Micro Labs Advanced Research Centre