Appendix I Project Plan Development Checklist I. R&D Plan a. Toxicology Plan Comments b. Regulatory Plan c. Documentation Plan (CMC) d. Marketing Plan II. Chemical Plan a. Chemical Availability b. Production Schedule c. ID. Comm. Manufacturing Process (Date) d. Impurities Identification and Qualification e. Solid State Characterization f. Stability Plan g. Release Testing h. Specification Setting III. Dosage Form Plan a. Development of Dosage Form Phase I Phase II Phase III/commercial Additional DF development b. Specification Setting C. Release Testing T. Catalano, Essential Elements for a GMP Analytical Chemistry Department, DOI: 10.1007/978-1-4614-7642-9, Ó Springer Science+Business Media New York 2013 181
Transcript
Appendix IProject Plan Development Checklist
I. R&D Plan
a. Toxicology Plan
Comments
b. Regulatory Plan
c. Documentation Plan (CMC)
d. Marketing Plan
II. Chemical Plan
a. Chemical Availability
b. Production Schedule
c. ID. Comm. Manufacturing Process (Date)
d. Impurities Identification and Qualification
e. Solid State Characterization
f. Stability Plan
g. Release Testing
h. Specification Setting
III. Dosage Form Plan
a. Development of Dosage Form Phase I Phase II Phase III/commercial Additional DF development b. Specification Setting
C. Release Testing
T. Catalano, Essential Elements for a GMP Analytical Chemistry Department,DOI: 10.1007/978-1-4614-7642-9,� Springer Science+Business Media New York 2013
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IV. Analytical Technology Plan
a. Development and validation of Analytical Methods
b. Prepare Technical Reports
c. Support Specifications Setting
d. Manage Stability Program
e. Support Formulation and Process Chemistry
f. Release Testing
V. Registration Plan
a. Preparation of Documents (CMC)
b. Finalize Reports
c. Identify Submission Date
d. Respond to Regulatory Responses
VI. Technology Transfer
a. Chemical Transfer
b. Dosage form Transfer
c. Analytical Methods Transfer
d. Create the Technology Transfer Team
e. Materials Sourcing Plan
182 Appendix I: Project Plan Development Checklist
Appendix IIProject Strategy Document
T. Catalano, Essential Elements for a GMP Analytical Chemistry Department,DOI: 10.1007/978-1-4614-7642-9,� Springer Science+Business Media New York 2013
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184 Appendix II: Project Strategy Document
Appendix II: Project Strategy Document 185
186 Appendix II: Project Strategy Document
Appendix IIIProject Risk Assessment
Risk factors analytical development
Weightings (1–10)
Risk factors Earlystage
Midstage
Latestage
Method development 3 6 9Method validation 2 9 10Availability of lots (DS &DP) 4 8 8PSA support 7 9 9Release testing 3 8 10QC release 3 8 10Manufacturing sites involvement 2 7 10Specifications 1 3 8Methods for alternative DF 1 7 8Method optimization 1 5 9Orthogonal methods 1 6 8Reference standard support 3 7 10Identification and qualification of impurities and degradationproducts
1 6 9
ICH validation 1 4 10Technology transfer 1 4 8Documentation, methods, validation Pkgs, regulatory, etc 3 6 10Development and technical reports 6 8 9Outsourcing 2 7 10Budget/resources/headcount 2 5 8Others
Weightings = 1 least Critical= 10 Most Critical
T. Catalano, Essential Elements for a GMP Analytical Chemistry Department,DOI: 10.1007/978-1-4614-7642-9,� Springer Science+Business Media New York 2013
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Risk factors pharmaceutical development
Risk factors Weightings (1–10)
Early stage Mid stage Late stage
Chemical and biological characterization 7 8 10Formulation characterization 2 8 10Manufacturability 2 5 10Excipient compatibility 3 7 10Formulation development 1 4 10Clinical plan 10 10 10Packaging 1 5 10Scale up and process optimization 1 2 10Manufacturing site changes 1 4 10Alternate dosage forms (Technology) 3 6 8Product definition 1 3 10Clinical supplies 1 10 10QC release 1 10 10Development stability 8 10 10Commercial process optimization 1 3 10Technology transfer 1 4 10Process validation 1 5 10Registration stability 1 5 10Commercial stability 1 5 10Documentation 10 10 10Outsourcing 10 5 3Budget 10 10 10Other
Weightings = 1 least Critical= 10 Most Critical
188 Appendix III: Project Risk Assessment
Risk Evaluation Data SheetRisk Factors Weight (1-10) X Rate (1-5) = Risk Value
Rating = 1 least Critical Total Risk Value (X) = = 5 Most Critical
Appendix III: Project Risk Assessment 189
Calculation of Plan Risk Evaluation
Calculate the Risk Evaluation using the following equations
1. Total risk evaluation%Rtð Þ ¼ ðxc � xminÞ
xmax � xmin� 100
2. Risk change index%Rcð Þ ¼ ðxn � xcÞ
xmax � xmin� 100
3. Low risk plan evaluation%RXLð Þ ¼ xL � xminð Þ
xmax � xmin� 100
Definitionsxmax Maximum total risk valuexmin Minimum total risk valuexL Total risk value for determined low risk planxc Total risk value for current planxn Total risk value for new plan%Rt Percent total risk of current plan%Rc Percent risk change between plans%RXL Percent risk evaluation of determined low risk planxmax - xmin The difference between the theoretical max. value and the theoretical min. value
190 Appendix III: Project Risk Assessment
About the Author
Dr. Tom Catalano’s has 30 years in the Pharmaceutical Industry in variouspositions including the Global Director of Analytical R&D, with major companiessuch as G. D. Searle, Pharmacia and Pfizer, which led to a multitude of experiencein providing analytical support to dosage forms and drug substances includingbiologicals. Additionally, he worked for a biopharmaceutical company,Theravance, as Sr. Director of Technical Operations.
He provided analytical support to a variety of dosage forms and drugsubstances, which included:
Tablets, Soft Capsules, Hard Capsules, Creams and GelsInjectables (Suspensions, Solutions or Lyophilized)Controlled Release Forms (Oral and Injectable)Manufacture of small molecules, peptides and proteinsIn Dr. Catalano’s 30 years in the industry, he made significant contributions to
the development and registration of many products such as NutraSweet, Cytotec,Arthrotec, Celebrex, Bextra, Dynastat, Inspra and Vibativ (glycopeptideantibiotic).
Currently Dr. Catalano is president of a consulting company, PharmChemAnalytical Consultants LLC.
T. Catalano, Essential Elements for a GMP Analytical Chemistry Department,DOI: 10.1007/978-1-4614-7642-9,� Springer Science+Business Media New York 2013
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Index
AAccuracy, 45, 127Analysis report, 158Analytical department interactions, 14Analytical project teams process, 5Analytical responsibilities, 13API in a bottle, 60API in a capsule, 62Arithmetic mean, 113Audit form, 140
HHighest level of authority, 12Hiring the best, 175HPLC method development, 28
T. Catalano, Essential Elements for a GMP Analytical Chemistry Department,DOI: 10.1007/978-1-4614-7642-9,� Springer Science+Business Media New York 2013
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IICH, 19Identification, 45Impurities and degradation products, 44Intent to transfer, 54Intermediate precision, 126Interviewer behavior, 176In vitro-in vivo correlation, 42Isocratic method development, 30
LLabeling, 26Laboratory operations, 16Least-squares linear regression, 119, 120Limit of detection (LOD), 128Limit of quantitation (LOQ), 129Linearity range, 44, 128
MManagement control, 17Mass balance, 44Master interview guide, 176Measurement uncertainty, 131Median, 114Mentoring program, 173Method familiarization, 55Method precision, 126Method qualification, 53Method transfer process, 56Method transfer protocol, 55Method validation, 43Method validation report, 153Modes of decision, 12Monitor execution of the plan, 6, 7
Process owners, 3Project plan, 15Project plan approval process, 7Project plan development process, 8Project strategy approval process, 7Project strategy development process, 6Project team dynamics, 8Project teams, 5Promotion process, 171Promotion process template, 172
RReference standard certification, 95Relative standard deviation, 115Repeatability, 126Request for quotation, 139Residual solvent, 45Risk evaluation, 7Robustness, 44Rounds of reasoning, 11Ruggedness, 130
SSafety process, 25Sample preparation, 37Sample replicates, 124Sample submission, 151Sampling strategies, 133Scribe, 12Significance testing, 113Simple random sampling, 134Sink conditions, 40Solvent handling, 27Solvent strength conversion, 31Specification development, 56Specification setting, 57Specificity, 44Specified degradation product, 95Specified impurity, 94Stability management, 87Stability report, 158Standard deviation, 114Standard error of the mean, 114Standard uncertainty (u), 132Statistical design of experiments, 123Sterile solution, 62Storage of all chemicals, 26
194 Index
Strategy document, 5Stratified random sampling, 135Stress testing, 94Student’s t distribution, 112Sub-sample, 134
