BPS2042 Drug Development HD 93 notes
Table of Contents
Structure of an NDA and TPP 2
Formulation Approaches 4
Product Specifications and SOPs 8
Pharmacopoeia, bioequivalence and biowaivers 12
Labelling & Packaging 16
Good manufacturing practice (GMP) 28
Preclinical PK studies: Ethics & Study selection 29
Preclinical toxicology 40
Clinical Trials 47
Drug approval process 62
Marketing and Intellectual Property 68
1
, BPS2042 Drug Development HD 93 notes
Structure of an NDA and TPP
- Goal: fully formulated, commercially viable, safe, and efficacious medicine
- Target Product Profile (TPP)
- Defines the minimal/ideal profile of the final marketed product and shows the
ultimate goals of the proposed therapy development effort
- E.g. disease indication, patient population, delivery mode, treatment
duration, treatment regimen, standards for clinical efficacy, delivery
mode, dosage form, regimen, efficacy, side effects, therapeutic area,
contraindications, drug interactions, storage and handling, warnings
and precautions, overdose, and potential for abuse, nonclinical
toxicology program, and patient counseling
- Not included in TPP but contain marketing information
- Primary markets, pharmacoeconomics, cost of goods, target
price, current gold standard, and possible product extensions
- Efficacy
- Determines PK/PD attributes by looking at magnitude and
duration of effect.
- Evaluation of molecular and formulation strategies to enable
oral absorption for low bioavailable drugs or to achieve
sufficient absorption for effect
- E.g. prodrugs
- Safety
- Considers dosing regimen and side effect profile
- Quality
2
, BPS2042 Drug Development HD 93 notes
- Defines acceptable shelf life dictated by the formulation
approach and packaging
- Defines quality testing requirements that can impact the
economics of the product and particular excipients
- New Drug Application (NDA)
- Presents complete known data for new medicinal products for the regulatory
authority to confirm their quality, safety, and efficacy.
- Vehicle where drug sponsors formally propose that the FDA approve a new
pharmaceutical for sale and marketing in the U.S.
- Goal: Provide enough information to permit an FDA reviewer to say:
- If the drug is safe and effective in its proposed use and if the benefits
outweigh the risks
- If the drug proposed labeling is appropriate and what it should contain
- If the methods used in manufacturing the drug and the controls used
to maintain the drug’s quality are adequate to preserve the drug’s
identity, strength, quality, and purity.
- NDA includes the ingredients of the drugs, the results of animal studies, how
the drug behaves in the body, what occurred during the clinical tests, and
how it is manufactured, processed, and packaged.
- Parts:
- Administrative Summary
- Chemistry, manufacturing, and controls (CMC)
- Preclinical studies
- Clinical studies
- Common Technical Document (CTD) / Modules of NDA
-
- Purpose: standardise documentation required for drug approval
3
, BPS2042 Drug Development HD 93 notes
- Terms
- Drug substance (S) - raw active ingredient used to make the drug
product e.g. 3.2.S.3
- Module 3 - provides information on the active ingredient
- Drug product (P) - drug product is the finished manufactured
medicine in its final packaging with its final label e.g. 3.2.P.5
Formulation Approaches
- Introduction
- The largest reason why drugs fail in development = pharmacokinetics
- Aim: obtain plasma levels within the therapeutic range for the required
period of time
- Oral administration of an immediate-release dosage form
- Therapeutic range = concentration interval between minimal effective
concentration (MEC) and minimal toxic concentration (MTC)
Route Typical Rationale Formulation/Typical Excipients
Dermal Treat condition on the skin Cream, ointment (Paraffin,
non-ionic surfactants, water,
preservative)
Transdermal Treat condition by systemic Gel - solvent, polymer, water;
absorption through the skin patch
Inhalation Local treatment of infection or Lactose (MDPI), propellant
inflammation in the lungs (nebuliser)
Intranasal spray Local treatment of infection of the Saline solution, pH control
nasal cavity or sinuses; systemic
absorption of drugs not orally
bioavailable
Intraocular Local treatment of infection or Saline solution, ointment,
topical inflammation of the cornea or suspension
tissues at the front of the eye
Intraaural Local treatment of ear canal Saline
Rectal Local treatment of infection or PEG, cocoa butter
suppository irritation of rectal mucosa, systemic
absorption where oral not possible
or preferred
Vaginal Local treatment of infection or Ointment, cream, mousse
irritation of the vaginal cavity
Sublingual/bucca Quick systemic onset Spray or patch
4
Table of Contents
Structure of an NDA and TPP 2
Formulation Approaches 4
Product Specifications and SOPs 8
Pharmacopoeia, bioequivalence and biowaivers 12
Labelling & Packaging 16
Good manufacturing practice (GMP) 28
Preclinical PK studies: Ethics & Study selection 29
Preclinical toxicology 40
Clinical Trials 47
Drug approval process 62
Marketing and Intellectual Property 68
1
, BPS2042 Drug Development HD 93 notes
Structure of an NDA and TPP
- Goal: fully formulated, commercially viable, safe, and efficacious medicine
- Target Product Profile (TPP)
- Defines the minimal/ideal profile of the final marketed product and shows the
ultimate goals of the proposed therapy development effort
- E.g. disease indication, patient population, delivery mode, treatment
duration, treatment regimen, standards for clinical efficacy, delivery
mode, dosage form, regimen, efficacy, side effects, therapeutic area,
contraindications, drug interactions, storage and handling, warnings
and precautions, overdose, and potential for abuse, nonclinical
toxicology program, and patient counseling
- Not included in TPP but contain marketing information
- Primary markets, pharmacoeconomics, cost of goods, target
price, current gold standard, and possible product extensions
- Efficacy
- Determines PK/PD attributes by looking at magnitude and
duration of effect.
- Evaluation of molecular and formulation strategies to enable
oral absorption for low bioavailable drugs or to achieve
sufficient absorption for effect
- E.g. prodrugs
- Safety
- Considers dosing regimen and side effect profile
- Quality
2
, BPS2042 Drug Development HD 93 notes
- Defines acceptable shelf life dictated by the formulation
approach and packaging
- Defines quality testing requirements that can impact the
economics of the product and particular excipients
- New Drug Application (NDA)
- Presents complete known data for new medicinal products for the regulatory
authority to confirm their quality, safety, and efficacy.
- Vehicle where drug sponsors formally propose that the FDA approve a new
pharmaceutical for sale and marketing in the U.S.
- Goal: Provide enough information to permit an FDA reviewer to say:
- If the drug is safe and effective in its proposed use and if the benefits
outweigh the risks
- If the drug proposed labeling is appropriate and what it should contain
- If the methods used in manufacturing the drug and the controls used
to maintain the drug’s quality are adequate to preserve the drug’s
identity, strength, quality, and purity.
- NDA includes the ingredients of the drugs, the results of animal studies, how
the drug behaves in the body, what occurred during the clinical tests, and
how it is manufactured, processed, and packaged.
- Parts:
- Administrative Summary
- Chemistry, manufacturing, and controls (CMC)
- Preclinical studies
- Clinical studies
- Common Technical Document (CTD) / Modules of NDA
-
- Purpose: standardise documentation required for drug approval
3
, BPS2042 Drug Development HD 93 notes
- Terms
- Drug substance (S) - raw active ingredient used to make the drug
product e.g. 3.2.S.3
- Module 3 - provides information on the active ingredient
- Drug product (P) - drug product is the finished manufactured
medicine in its final packaging with its final label e.g. 3.2.P.5
Formulation Approaches
- Introduction
- The largest reason why drugs fail in development = pharmacokinetics
- Aim: obtain plasma levels within the therapeutic range for the required
period of time
- Oral administration of an immediate-release dosage form
- Therapeutic range = concentration interval between minimal effective
concentration (MEC) and minimal toxic concentration (MTC)
Route Typical Rationale Formulation/Typical Excipients
Dermal Treat condition on the skin Cream, ointment (Paraffin,
non-ionic surfactants, water,
preservative)
Transdermal Treat condition by systemic Gel - solvent, polymer, water;
absorption through the skin patch
Inhalation Local treatment of infection or Lactose (MDPI), propellant
inflammation in the lungs (nebuliser)
Intranasal spray Local treatment of infection of the Saline solution, pH control
nasal cavity or sinuses; systemic
absorption of drugs not orally
bioavailable
Intraocular Local treatment of infection or Saline solution, ointment,
topical inflammation of the cornea or suspension
tissues at the front of the eye
Intraaural Local treatment of ear canal Saline
Rectal Local treatment of infection or PEG, cocoa butter
suppository irritation of rectal mucosa, systemic
absorption where oral not possible
or preferred
Vaginal Local treatment of infection or Ointment, cream, mousse
irritation of the vaginal cavity
Sublingual/bucca Quick systemic onset Spray or patch
4
