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SUPPLEMENTAL NEW
DRUG APPROVAL PROCESS
(SNDA)
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Manufacturer of new drug applications (NDAs) and abbreviated new drug applications
(AND2As) who intend to make post approval changes can do so in accordance with section
506A of the Federal Food, Drug, and Cosmetic Act (the Act) and § 314.70 (21 CFR 314.70).
Post-approval changes can be categorized and applied in below mentioned categories:
1. Components and composition,
2. Manufacturing sites,
3. Manufacturing process,
4. Specification,
5. Container closure system,
6. Labeling, as well as
7. Miscellaneous changes, and
8. Multiple related changes.
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Section 506A of the Act and § 314.70 provide for four reporting categories as mentioned
belo3w:
A major change is a change that has a substantial potential to have an adverse effect on the
identity, strength, quality, purity, or potency of a drug product as these factors may relate
to the safety or effectiveness of the drug product. A ma change requires the submission of
a supplement and approval by FDA prior distribution of the drug product made using the
change.
This type of supplement is called, and should be clearly labeled, a prior approval
supplement ($ 314.700 An applicant may ask FDA to expedite its review of a prior approval
supplement for public health reasons (e.g. drug shortage) or if a delay in making the
change e described in it would impose an extraordinary hardship on the applicant. This
type of supplement is called, and should be clearly labeled, a prior approval supplement
expedited review requested (§ 314.70(b)(4)).
A moderate change is a change that has a moderate potential to have an adverse effect on the
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identity, strength, quality, purity, or potency of the drug product as these factors may relate to
the saf4ety or effectiveness of the drug product.
There are two types of moderate change. One type of moderate change requires the submission
of a supplement to FDA at least 30 days before the distribution of the drug product made using
the change.
This type of supplement is called, and should be clearly labeled, a supplement-changes being
effected in 30 days (§ 314.70©(3)). The drug product made using a moderate change cannot be
distributed if FDA informs the applicant within 30 days of receipt of the supplement that a prior
approval supplement is required (§ 314.70©(5) (i)).
for each change, the supplement must contain information determined by FDA to be appropriate
and must include the information developed by the applicant in assessing the effects of the
change (§ 314.70(a)(2) and ©(4)). If FDA informs the applicant within 30 days of receipt of the
supplement that information is missing, distribution must be delayed until the supplement has
been amended to provide the missing information (§ 314.70© (5)(ii)).
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A minor change is a change that has minimal potential to have an
adverse effect on the identity, strength, quality, purity, or potency
of the drug product as these factors may relate to the safety or
effectiveness of the drug product. The applicant must describe
minor changes in its next Annual Report (§ 314.70(d)).
The FDA has issued guidance document on scale-up post-approval changes (SUPAC). SUPAC is
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most significant guidance issued by US FDA and help this guidance is greatly welcomed by the
industr6y because gives a very clear and straight idea for handling the post approval changes and
greatly reduces the approval timeline. Dosage forms covered under the SUPAC guidelines are
mentioned below:
1. Immediate release (IR) solid oral dosage form.
2. Modified release (MI) solid oral dosage forms, Le extended release, delayed release
3. Non sterile serd-solid (55) dosage forms, i.e creams, ointments, suspensions,emulsions, gels
and lotions.
Levels of change defined under SUPAC
Level 1: Unlikely to have impact on the product. Filed as an annual report update, normal
testing as filed in NDA.
Level 2: Moderate changes such as technical grade of inert, filed as CBE or PA. accelerated
stability and dissolution profile testing in addition to filed NDA.
Level 3: Likely to have impact, filed PA, stability and testing as above in addition a biostudy or in
vivo correlation.
The SUPAC guidance mainly provides the guidance (though not the complete list, but
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some important aspects) on below mentioned changes:
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❑ Manufacturing site change
❑ Batch size change
❑ Manufacturing process change
❑ Manufacturing equipment change
❑ Analytical testing site change
❑ Packaging site change
composition-non-release controlling excipient
And composition-release controlling excipient
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