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ATMP Sweden Process map Clinical Process Map

Clinical Process Map

Welcome to the landing site for the ’Clinical needs’. Your role is to ensure that the medical need behind the product is valid, that patients can be screened/recruited and that hospital infrastructures for implementation are in place, for collecting donor material, running clinical trials, interacting with industry and delivering market approved medicines. You also have an important role in ensuring healthcare budgets are suited to accepting curative, one time ATMP treatments.

Below you can see our ’process map’ that shows what you need to be considering at what stage of ATMP development. There are other process maps for manufacture, regulatory, product developer and commercial needs, that can give you tips on how to address these needs in your team. The objective here is to have the right people considering the right things at the right time to ensure that your ATMP pipeline moves forward as effectively as possible, good for patients in need, good for your pocket to not waste money and time on inefficiencies.

Clinical

  • 1. Process Development

  • 2. Process Qualification

  • 3. GMP Manufacturing

  • 4. Clinical Trials

  • 5. Market Approval and Reimbursement

  • 6. Standard of Care

Process Development

  • Unmet clinical need
  • Clinical strategy Ph I/II/III patient populations and trial size.  Identify efficacy. Consult MPA
  • Proper identification of the patient group, the realistic size of the group and the anticipated time line for completing a study when applying inclusion/exclusion criteria and logistics. It is not rare that the list of eligible patients is not as long as anticipated when all factors for possible inclusion and treatment are fulfilled.
  • Means for transport/storage/handling in clinical setting. 
  • Delivery device – MPA product/CE marked.
  • Optimise product for clinical success
  • Identify clinically relevant mutations for start material, product and disease
  • Strategies to avoid immune rejection or unwanted side effects.
  • Identify clinically suitable tools/devices
  • In vitro v in vivo dose response assays
  • Identify suitable human biomarkers for measuring safety and efficacy
  • Clinical suitability of donor testing, health declaration
  • Tissue procurement suitability for pharmaceutical manufacture. Sustainability of procurement.
  • Quality agreement with MPA/LV tissue establishment
  • Pseudonymisation and labelling of material to enter an MPA/LV tissue establishment
  • Appropriate formulation/composition for drug product and dose preparation. Pharmaceutical grade components?
  • Determine route of administration and delivery device
  • After discussion with regulatory bodies, determine preclinical safety studies
  • GDPR requirements in regard to donor consent, testing and start material

Process Qualification

  • Identify and prepare suitable clinic for dose preparation and in use stability
  • Clinical site accreditation
  • GCP for ATMPs
  • Clinical trials and animal study design – consult MPA
  • Clinical trials permit
  • Hospital ATMP centre engagement – hospital pharmacy function priority and preparation advice
  • MPA permit to dispense and dose prepare pharmaceutical
  • Hospital ’studieråd’ clinical trials study council 

Product Manufacture

  • Discuss CTA with MPA
  • Clinical Trial Application submission with safety/release data on clinical product
  • Arbetsmiljöverket application for gene therapy clinical trials – clinic and pharmacy
  • Develop informed consent for trial participants
  • Clinical Study Protocol
  • Clinical trial authorisation
  • Ethics approval sponsor and site
  • Validate transport, hospital pharmacy intake
  • Validate dose preparation and delivery dose. 
  • Effect data

Clinical Trials

  • Hospital implementation and clinical trial
  • Patient recruitment
  • Patient consent
  • Patient reported outcomes
  • Safety First In Human
  • Dose finding, size and number, tolerable dose, (side effects) v effective dose
  • Documenting efficacy and relevance – comparison to something (placebo, SOC)
  • E-CRF (electronic case report form) – safety data, medical history

Market Approval and HTA

  • Cost/benefit versus existing treatments
  • NT-Rådet informs hospital pharmacy of health economic evaluation to accelerate patient access
  • Hospital pharmacy routines for transport, storage, equipment, capacity, procurement, cost followup
  • Quality and delivery agreements between hospital and pharmacy function
  • Engaging healthcare leadership and KOL to establish national infrastructure ’Marknadsavtal’

Clinical Routine

  • Secure health budget and implement
  • Region allocates budget 
  • Develop process for treating patients – requirements from EMA and accreditation requirements
  • Treatment guidelines 
  • Register (national and international)
  • Hospital pharmacy requests from distributor
  • Hospital pharmacy receives and dose preparation
  • Collection and reporting of data for conditional approval
  • Safety and pharmacovigilance reporting
  • Cost effective treatment provided
  • side effects, reporting, followup