Development Pharmaceutics

Dr. Pogány | April 20081 |

Pharmaceutical Development with Focus on Paediatric Formulations


WHO/FIP Training Workshop Hyatt Regency Hotel

Sahar Airport Road

Andheri East, Mumbai, India

28 April 2008 – 2 May 2008




Presented by:

Name: Dr. János Pogány

Contact details:

[email protected]


Outline of presentationOutline of presentation

Regulatory issues in Regulatory issues in development pharmaceuticsdevelopment pharmaceutics

Differences between the pharmaceutical development process of innovator and multisource (generic) FPPs

WHO draft guideline on Pharmaceutical Development

– Initial quality risk assessment

– Multisource pharmaceutical product development

– Pharmaceutical manufacturing process development

Conclusions


Pharmaceutical product target profile (PPTP)Pharmaceutical product target profile (PPTP)

Innovator FPPInnovator FPP

Bioavailability and dosage regimen are established during Phase I-II clinical trials

PPTP will be achieved through clinical studies to ensure the required quality focused on safety and efficacy

Generic FPPGeneric FPP

Bioavailability, pharmaceutical form and strength are known. PPTF is the innovator FPP.

PPTP is achieved through demonstration of pharmaceutical equivalence and bioequivalence


Differences in pharmaceutical developmentDifferences in pharmaceutical development


Composition

Manufacturing method should be selected

Container closures system (delivery device) of the FPP should be experimentally developed


Qualitative composition of innovator FPP is known from regulatory websites (EMEA and US-FDA)

Manufacturing method is determined by the composition and the dosage form of the innovator FPP

Qualitative characteristics of primary packing materials are known.


Differences in pharmaceutical developmentDifferences in pharmaceutical development


API specifications are developed and contain the user requirements for manufacturability

Shelf life and special storage conditions come from research


API specifications are typically available but user requirements should be established experimentally

Target values are known


Qualification Stage Validation Stage

Key elements D & C Installation Operation Prospective Concurrent

Facilities and Engineering phase Manufacturing Start-Up

Equipment

(Validation Protocols) (Batch Records and Validation documentation)

Target profile Design (laboratory) Scale-Up (pilot plant) Production

(Bench marking (Critical Q attributes, (Critical process (Final batch size,

of innovator formula screening, parameters, primary process

product) process design ) batches) controlled)

Generic product and process development

Generic pharmaceutical developmentGeneric pharmaceutical development

CONTINUOUS IMPROVEMENT


Development strategyDevelopment strategy

INTERCHANGEABILITY (IC)INTERCHANGEABILITY (IC) OF GENERIC FPPs =

THERAPEUTICAL EQUIVALENCE WITH A

COMPARATOR (REFERENCE) FPP =

PHARMACEUTICAL EQUIVALENCEPHARMACEUTICAL EQUIVALENCE (PEPE) +

BIOEQUIVALENCE (BE) ICIC = PEPE + BE

The best strategy for generic product development is to use the same qualitative and quantitative formula as that of the comparator (reference/innovator) FPP


WHO draft guidance on Pharmaceutical Development WHO draft guidance on Pharmaceutical Development

Section 3.2 (3.2.P.2 in CTD) in the „Guideline on Submission of Documentation for Prequalification of Multi-source (Generic) Finished Pharmaceutical Products (FPPs) Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis” contains a section 3.2 Pharmaceutical Development but the contents do not provide sufficient details either for the Applicants or the Assessors.

The ICH Q8 guideline describes a development process with new FPPs in mind and only partially applies to generic FPPs.


Pharmaceutical Development with Focus on Paediatric formulations


WHO working document QAS/07….

DRAFT PHARMACEUTICAL DEVELOPMENT FOR MULTISOURCE (GENERIC) PHARMACEUTICAL PRODUCTS

INITIAL QUALITY-RISK ASSESSMENTINITIAL QUALITY-RISK ASSESSMENT


Initial quality risk assessment - Desk researchInitial quality risk assessment - Desk research

Nevirapine is lipophilic (partition

coefficient 83) and is essentially

nonionized at physiologic pH.

As a weak base (pKa 2.8), Nevirapine is

showing increased solubility at acidic pH

values.

Source: Merck Index

Aqueous solubility (anhydrate) (90μg/ml at

25°C).

Nevirapine is highly stable


Viramune 50 mg/5 ml oral suspensionViramune 50 mg/5 ml oral suspension Oral suspension containing 10 mg/ml of nevirapine as 10.35 mg/ml NNevirapineevirapine

HHemihydrateemihydrate as the API. ExcipientsExcipients: Carbomer, methyl parahydroxybenzoate, propyl parahydroxybenzoate,

sorbitol, sucrose, polysorbate 80, sodium hydroxide and purified water. (FDA excipient list: Carbomer 934P).

Shelf lifeShelf life: 3 yearsThe product should be used within 2 months of opening2 months of opening.

No special precautions for storage Nature and contents of containerNature and contents of container White HDPE bottle with two piece child-resistant

closure (outer shell white HDPE, inner shell natural polypropylene) with LDPE foam liner. Each bottle contains 240 ml of oral suspension.Clear polypropylene 5-ml dispensing syringedispensing syringe (0.2 ml graduations) with silicone rubber piston seal.Clear low density polyethylene bottle-syringe adapter.bottle-syringe adapter.http://www.emea.europa.eu/humandocs/PDFs/EPAR/Viramune/109697en6.pdf http://www.fda.gov/cder/ogd/rld/20933s3.PDF

Nevirapine oral suspension monograph (PhInt) has reached a draft stagemonograph (PhInt) has reached a draft stage


Viramune 50 mg/5 ml oral suspensionViramune 50 mg/5 ml oral suspension The HDPE bottleHDPE bottle material is inert and was shown to be compatiblecompatible with

the active substance and other ingredients of the formulation.

The levels of preservatives have been correlated with antimicrobial antimicrobial effectivenesseffectiveness tested according to PhEur

Acceptable data demonstrating the precision and accuracy of the dosing syringe were provided.

Synthesis impurities are not degradants Synthesis impurities are not degradants and not part of FPP specifications

The method of preparation of the oral suspension is standard for this form and has been adequately described. Validation data presented on three production batches manufactured using three differentthree different lots of nevirapinelots of nevirapine anhydrous (?)(?) were adequate to demonstrate that the process is under control and ensures both batch-to-batch reproducibility and compliance with standard specifications. Tests Tests atat release are standard and ensure release are standard and ensure reproducible clinical performance of the product.reproducible clinical performance of the product.


Viramune 50 mg/5 ml oral suspensionViramune 50 mg/5 ml oral suspension

StabilityStability data up to 18 months for the newly recapped oral suspension and 24 months with the old pulpboard liner confirmed the physical and chemical stability of the oral suspension and the antimicrobial efficacy of the preservative. These results support a shelf life of 24 monthsresults support a shelf life of 24 months. Long-term stability data will be submitted on ongoing basis.

An in-use stability studyin-use stability study designed to mimic the delivery of 2 ml dose, which represents one of the lowest projected doses, twice a day, using the delivery device intended for marketing has been performed.

An additional studyadditional study is presented on the stability of the product exposed to freeze-thawfreeze-thaw conditionsconditions. On the basis of results from both studies, the claimed in-use shelf life of 60 daysin-use shelf life of 60 days with no special storage precautions is supported.


Viramune - Clinical informationViramune - Clinical information Nevirapine was readily absorbed (> 90 %) after oral administration in healthy

volunteers and in adults with HIV-1 infection.

A 3-way crossover study compared the bioavailability from three production/commercial scale batches with varying dissolution profiles. All three batches were bioequivalent with respect to systemic exposure (AUC). The significantly different values for Cmax and tmax were considered not to be clinically relevant.

In studies 1100.1231 and 1100.896 in which the suspension was administered directly using a syringe, it was demonstrated that the suspension and tablet the suspension and tablet formulations were comparably bioavailableformulations were comparably bioavailable with respect to extent of absorption. In study 1100.1213 the suspension was administered in a dosing cup without rinsing. The suspension intended for marketing was bioequivalent to the suspension used during clinical trials but was not bioequivalent to the marketed not bioequivalent to the marketed tabletstablets.. This could be attributed to incomplete dosing of the two suspensions since there was about 13 % of the dose remaining in the cup.


Viramune - Clinical informationViramune - Clinical information It has been later determined in a single dose study in 9 patients aged between 9

months and 14 years administered after an overnight fast (3 patients per dose level equivalent to 7.5 mg/m², 30.0 mg/m² and 120.0 mg/m²).

Based on adult experience, a comparable lead-in period of two weeks was suggested for pediatric population. A 4 mg/kg dose is proposed for all children regardless the age. Although no particular study has been performed to find the optimal lead-in dose, this dose was considered acceptable considering the enzyme induction to achieve initial antiretroviral activity.

The final recommended doses for the different ages are therefore the following:

Patients from 2 months to 8 years, 4 mg/kg once daily for 2 weeks followed by 7 mg/kg bid

Patients from 8 years to 16 years are 4 mg/kg once daily followed by 4-mg/kg bids.


Initial quality risk assessment - ExperienceInitial quality risk assessment - Experience

Not critical to Q Potentially critical to QMonitoring

strategy

Critical to QControl strategy

Milling API

Weighing Wetting

API Vehicle

Wet milling

Filling Packing

Dissolution Assay Degradation Content uniformity

Stability physical microbial pH

delete






DEVELOPMENT and VERIFICATION of ANALYTICAL METHODS

DEVELOPMENT and VERIFICATION of ANALYTICAL METHODS


Product-specific analytical methodsProduct-specific analytical methods

Analytical test methods help identify the acceptable ranges of critical quality attributes [CQA(s)] and critical process parameters [CPP(s)] of laboratory and pilot-scale product and process development experiments – ICH guidelines with non-compendial APIs and FPPs

In-house reference standards should be established at the start of the development process and they should be qualified against compendial reference standards – Special issues with first-time generic FPPs

A discriminatory dissolution method should be developed and validated at an early stage


Innovator FPP Generic FPP

Dissolution test3 batches

Production batch, orNLT 1/10 of final size

Reference product Test product

Select a batch showing intermediate dissolution

Dissolution (and bioequivalence) batchDissolution (and bioequivalence) batch

Dissolution profile


Role of dissolution testingRole of dissolution testing

To determine if a dissolution method can discriminatediscriminate product changes, the method must be challenged.

Dissolution profile testing for solid oral dosage forms supports pharmaceutical development and regulatory decisions

– Formulation screening and dissolution equivalence– In vitro bioequivalence test method – Waiver for in vivo bioequivalence studies– Stability studies– Variations to the prequalified dossier

It is primarily a QC tool to verify process and product consistency (if an in vitro-in vivo correlation (IVIVC) has not been established)


Discriminatory power – 2FDC productDiscriminatory power – 2FDC product

0

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Withdrawal time in minutes

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Experiment B


Discriminatory power– 2FDC productDiscriminatory power– 2FDC product

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Experiment C

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Experiment D


Discriminatory power – 2FDC productDiscriminatory power – 2FDC product

All 4 productsAPI: Isoniazid

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All 4 productsAPI: Ethambutol

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Dis

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%)

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B,C

D

All 4 experiments, API 1

All 4 experiments, API 2


Establishment of dissolution specificationsEstablishment of dissolution specifications

The in vitro specifications in vitro specifications for generic products should be should be established based on a dissolution profilebased on a dissolution profile.

Dissolution specifications should be based on acceptableacceptable clinical, bioavailability, and/or bioequivalence batchesbioequivalence batches.

In the case of a generic drug product, the dissolution specifications are generally the same as the reference listed reference listed drugdrug.

Once a dissolution specification is set, the drug product should drug product should comply with that specification throughout its shelf lifecomply with that specification throughout its shelf life.


WHO guidelines on dissolutionWHO guidelines on dissolution

Annex 7 - Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability, in WHO TRS, No. 937, 2006

Annex 8 - Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms (ibid)

Annex 11 - Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products, in WHO Technical Report Series, No. 902, 2002

Annex 5 - Guidelines for registration of fixed-dose combination medicinal products, in WHO TRS, No. 929, 2005






PRODUCT DEVELOPMENTPRODUCT DEVELOPMENT


Innovator suspension – target profile (1)Innovator suspension – target profile (1)

Each ml of oral suspension contains:

10 mg of nevirapine (as hemihydrate)

Carbomer 934P

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Sorbitol

Sucrose

Polysorbate 80

Sodium hydroxide (for pH-adjustment)

Purified water

http://www.emea.europa.eu/humandocs/PDFs/EPAR/Viramune/H-183-PI-en.pdf


Light microscopic images of a suspensionLight microscopic images of a suspension

Stable suspension Aggregated suspension

Moorthaemer and Sprakel: Improving the stability of a suspension, Pharm. Techn. Europe, Feb. 2006


Adsorption isotherm of a surfactantAdsorption isotherm of a surfactant

Moorthaemer and Sprakel: Improving the stability of a suspension, Pharm. Techn. Europe, Feb. 2006


Surfactant concentrationSurfactant concentration

Three formulations containing 50 mg, 25 mg of sodium laurylsulfate (SLS) and no SLS, were evaluated in the dissolution medium. The dissolution profile of the formulation containing no SLS showed incomplete solubilization of celecoxib (CEL), a poorly soluble API. Addition of even 25 mg of SLS into the formulation drastically improved the dissolution of CEL.

Source: Bansal, A. K.: Criticality of functional excipients … Pharmaceutical Technology Europe, June 2006


Innovator suspension – target profile (2)Innovator suspension – target profile (2) Sample confirmationSample confirmation

– Batch numbers– Shelf life: 3 years and within 2 months of opening2 months of opening.– Storage instructions: No special precautions for storageNo special precautions for storage– Container and closure system: as per EPARas per EPAR

QC analysisQC analysis (hypothetical figures)hypothetical figures)– Assay: 99.9% of labelled amount (LA)– Methylparaben (HPLC): 0.18% w/v– Propylparaben (HPLC): 0.02% w/v– Total related substances: 0.03%– Specific gravity (at 25oC): 1.150 – Viscosity (at 25oC): 1,150 cPs– pH: 5.80


Innovator suspension – target profile (3)Innovator suspension – target profile (3)

The composition suggests that:

Sucrose and sorbitol are used to adjust the density of the medium

Carbomer 934P is used to adjust viscosity

Polysorbate 80 is a wetting agent

Sodium hydroxide is used to adjust the pH to 5.8


Innovator product – target profile (4)Innovator product – target profile (4)

Time (minutes)% API dissolved (hypothetical figures)(hypothetical figures)

527

1042

1555

2065

3076

4588

6092

Dissolution profile (% LA)

Apparatus: USP II (paddle, 25rpm)

Medium: 0.1N HCl

Volume: 900ml http://www.accessdata.fda.gov/scripts/cder/dis

solution/dsp_SearchResults_Dissolutions.cfm


Innovator product – target profile (5)Innovator product – target profile (5)

Time (minutes)% API dissolved (hypothetical figures)

% API dissolved (hypothetical figures)

% API dissolved (hypothetical figures)

pH 1.2 bufferpH 4.5 bufferpH 6.8 buffer

5271522

10422527

15553635

20654242

30764849

45884957

60924965

901005076Dissolution profile (% LA), Apparatus: USP II (paddle, 25rpm), Volume: 900ml – Different speeds to be investigated


Pharmaceutical development protocolPharmaceutical development protocol API experimentsAPI experiments

– Solubility at 37 oC– Particle size distribution– Density

Formulation experimentsFormulation experiments– Screening laboratory batches with different proportions of excipients to match

innovator dissolution– Stress testing of the selected composition – Compatibility with excipients – Antimicrobial effectiveness test according to PhEur

Packing materialsPacking materials– Dimensions and tolerances of packing components– Precision and accuracy of the dosing syringe


Product-specific physical API propertiesProduct-specific physical API properties

Introduction of

the API starting

materials into

process

Production

of intermediate(s)

Isolation and

purification

Physical processing and

packaging

PhInt specifications + residual solvents from APIMF.Product-specific physical properties depend on crystallization and subsequentphysical processing. Density and particle size distribution of Nevirapine Hemihydrate are critical quality attributes of the API. Acceptance criteria are established by measurement of particle size of innovator’s API in suspension and through the similarity of dissolution profiles of innovator and generic products.


Solubility of nevirapine hemihydrate at 37oCSolubility of nevirapine hemihydrate at 37oCpHDissolved material (mg/ml)

(hypothetical figures)

1.22.75

2.10.28

3.00.08

4.50.06

6.80.06

7.20.06

8.00.06

Nevirapine Hemihydrate belongs to BCS Class 2 (low solubility, high permeability).

Solubility data are also important for cleaning validationSolubility data are also important for cleaning validation


Water sorption isotherm of Ethambutol•2H2OWater sorption isotherm of Ethambutol•2H2O

Water uptake in 24 hours at a temperature of 25oC ± 2oC

45% RH: 0%

60% RH: 0%

80% RH: 3.31 to 5.18%


Dissolution profiles of innovator and generic FPPsDissolution profiles of innovator and generic FPPs

Mean % API

dissolved

Time (minutes)

▀ innovator

▀ generic

Similarity factor, f2=73

0

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0 10 20 30 40 50 60 70 80 90


Selected generic composition (hypothetical figures)Selected generic composition (hypothetical figures)

Ingredients mg/5mlNevirapine hemihydrate 51.7

Excipients– Carbomer 934P 8.0– Methyl parahydroxybenzoate 10.0 – Propyl parahydroxybenzoate 1.0– Sorbitol 800.0– Sucrose 700.0– Polysorbate 80 3.0– Sodium hydroxide q.s.– Purified water to make 5.0 ml


Compatibility with excipientsCompatibility with excipientsNevirapine Hemihydrate in solid state – illustrative exampleillustrative example: heat

Stress Condition

Treatment Observations Assay: SI1: D1: Total unspecified:

None Initial values API

Total impurities: Assay: SI1: D2: Total unspecified:

Heat

API is mixed with excipient, the mixture is wetted and a thin layer of the powder blend is kept at 60°C for 4 weeks in a Petri dish (open system) Total impurities:

To do: sstress testingtress testing the dose-proportional mixture of the APIs in in aqueous mediumaqueous medium.


Container and closure systemContainer and closure system

Primary packing materials for the comparator FPP are recommended. Plastic materials should comply with relevant pharmacopoeial and food contact regulations.

Market specific needs (e.g., Climatic Zone IVb) and patient handling needs (hygienic and pilfer-proof blister cards) should be taken into account.

Stability testing of primary batches should be conducted in the selected markets packs.

When the container and closure system is a critical factor of FPP stability, batch or supplier variations should be minimized through tight specifications and extended sampling plans for QC testing.


Proposed FPP specificationsProposed FPP specifications Description Identification (HPLC) Dissolution (UV): Q = 70% in 45 minutes pH = 4.8 – 6.2 Deliverable volume

– Average fill volume: NLT 240 ml– Fill volume variation: should meet Ph. Int. requirements

Related substances: not testednot tested Preservative content (HPLC)

– Methylparaben: 98 to 102% of LA [End of shelf life: 80 to 102% of LA]– Propylparaben: 98 to 102% of LA [End of shelf life: 80 to 102% of LA]

Assay: 95.0 to 105.0% of LA

End-of shelf-life acceptance limits for assay should not be proposed at this stage.End-of shelf-life acceptance limits for assay should not be proposed at this stage.






PROCESS DEVELOPMENTPROCESS DEVELOPMENT


Key termsKey terms

Critical Quality Attribute (CQA):A physical, chemical, biological or microbiological property or

characteristic (of starting materials and intermediatesof starting materials and intermediates) that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

Critical Process Parameter (CPP):A process parameter whose variability has an impact on a (or

more) critical quality attribute(s) and therefore should be monitored or controlled to ensure that the process produces the desired quality.


Key termsKey terms

Proven Acceptable Range (PAR): „A characterised range of a process parameter range of a process parameter for which operation within

this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria.”

Design Space (DS): „The multidimensional combination and interaction of input variables The multidimensional combination and interaction of input variables

(e.g., material attributes) and process parameters (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.”


Design range and design spaceDesign range and design space

Design space determined from the common region of successful operatingranges for multiple CQAs. The relations of two CQAs, i.e., friability and dissolution, to two interacting process parameters (e.g., impeller speed and spray rate) of a granulation operation are shown in Figures 1 and 2 (from left to right).Figure 3 shows the overlap of these regions and the maximum ranges of the potential design space.


Regulatory expectations on process developmentRegulatory expectations on process development Selection of process: standard for oral aqueous suspensions The progress from pre-formulation (size:1x) → formulation (10x) → pilot

manufacture (100x but not less than 1/10th of production batch) → production scale (approved batch size) manufacture should be shown in the dossier submitted for prequalification to be logical, reasoned and continuous.

A pilot pilot batchbatch is manufactured by a procedure fully representative ofa procedure fully representative of and simulating that to be applied to a full production scale batch.

Manufacture of primary batchesprimary batches in the proposed container and closure systems for:

– Bioequivalence and dissolution studies from the same batch– Regulatory stability studies ( including in-use stability study and an additional study

under freeze-thaw conditions.)– Prospective validationvalidation of bioequivalencebioequivalence, dissolutiondissolution and stability batchesstability batches


Scale up activitiesScale up activitiesStability protocolStability protocol is prepared A large number of samples is tested from pilot scale batches A large number of samples is tested from pilot scale batches to

establish provisional acceptance limits for the control of critical process parameters (prospective validation, IPC limits) in order to define design space (process knowledge)(process knowledge) and control strategycontrol strategy (risk mitigation)(risk mitigation) that encompasses aspects of scale, environmental aspects of site, packaging, as well as final product stability.

Validation protocolValidation protocol is writtenDossier is submitted Dossier is submitted for prequalification


Prospective validationProspective validation

The manufacturing process used for primary batches should simulate that to be applied to production batches and should provide product of the same quality and meeting the same specification as that intended for marketing.

Based on monitoring closely the manufacturing process of primary batches, provisional acceptance ranges should be proposed for the CQAs of intermediates and CPPs that impact on downstream processing. Interim acceptance criteria may be approved until enough knowledge is available to finalize CQAs of intermediates and CPPs.

Manufacturing control strategy is proposed for the mitigation of quality risks


High-shear batch mixer and in-line mixerHigh-shear batch mixer and in-line mixer


General principlesGeneral principles

A process is well understood when:– all critical sources of variability have been identified and explained

– variability is managed by the process

– product quality attributes can be accurately and reliably predicted

All critical process parameters should be identified, monitored or controlled to ensure that the product is of the desired quality

The manufacturing process of the generic FPP should be the same as that of the reference FPP


Objective and result of process controlObjective and result of process control

UCL

N

LCL

UCL

N

LCL

UCL

N

LCL

1.The process reveals serious risks and it is not controlled

2.The process is not yet controlled but acceptance criteria are met

3.The process is under control and the product has a consistently high quality


Process under controlProcess under control

Most points fall near the central line (68% within one σ)

A few points fall near the control limits (5% in the third σ)

Points shold balance on both sides of the mean

Points should cross the mean line often

Points should show a random pattern (no trends, cycles, clustering)


ICH Q9 - Annex I.9: Supporting statistical toolsICH Q9 - Annex I.9: Supporting statistical tools

Process Capability AnalysisEstimate the potential percent of defective product

Cp value cp=0.5 cp=1 cp=3

graphical view of different cp values

UGW OGW

UGW OGW

UGW OGW

values statistically out of limit

13,58 % 0,27 % approx. 0

values in the limit

86,42 % 99,73 % > 99,999999 %

Result: process statistically

out of control process statisticaly under control


Main points againMain points again Pharmaceutical development isPharmaceutical development is an essentialessential part of applications for

prequalification. Guidance is needed also for those Applicants and DRAs that do not use the ICH Q8 guideline.

Desk research Desk research gives valuable information for generic pharmaceutical product and process development

FPP-specific quality and processability requirements FPP-specific quality and processability requirements are integrated into the API specifications during pharmaceutical development studies.

Dissolution profile testingDissolution profile testing plays a key role in establishing pharmaceutical equivalence

A science- and risk-based pharmaceutical development science- and risk-based pharmaceutical development of generic FPPs provides a high level of assurance for interchangeability provides a high level of assurance for interchangeability with the innovator product.

Manufacturing process design and optimization Manufacturing process design and optimization identifies the critical attributes whose control leads to the batch-to-batch consistency of quality


THANK YOU!THANK YOU!

Development Pharmaceutics

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